Lung Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

LUNG DISEASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Lung Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84018-0 1. Lung Disease-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on lung disease. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON LUNG DISEASE .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lung Disease................................................................................. 8 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 67 CHAPTER 2. NUTRITION AND LUNG DISEASE .............................................................................. 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Lung Disease.............................................................................. 113 Federal Resources on Nutrition ................................................................................................. 115 Additional Web Resources ......................................................................................................... 115 CHAPTER 3. DISSERTATIONS ON LUNG DISEASE .......................................................................... 117 Overview.................................................................................................................................... 117 Dissertations on Lung Disease .................................................................................................. 117 Keeping Current ........................................................................................................................ 118 CHAPTER 4. CLINICAL TRIALS AND LUNG DISEASE .................................................................... 119 Overview.................................................................................................................................... 119 Recent Trials on Lung Disease .................................................................................................. 119 Keeping Current on Clinical Trials ........................................................................................... 134 CHAPTER 5. PATENTS ON LUNG DISEASE..................................................................................... 137 Overview.................................................................................................................................... 137 Patents on Lung Disease............................................................................................................ 137 Patent Applications on Lung Disease ........................................................................................ 150 Keeping Current ........................................................................................................................ 164 CHAPTER 6. BOOKS ON LUNG DISEASE ........................................................................................ 167 Overview.................................................................................................................................... 167 Book Summaries: Federal Agencies............................................................................................ 167 Book Summaries: Online Booksellers......................................................................................... 168 The National Library of Medicine Book Index ........................................................................... 173 Chapters on Lung Disease ......................................................................................................... 175 CHAPTER 7. MULTIMEDIA ON LUNG DISEASE ............................................................................. 179 Overview.................................................................................................................................... 179 Bibliography: Multimedia on Lung Disease .............................................................................. 179 CHAPTER 8. PERIODICALS AND NEWS ON LUNG DISEASE .......................................................... 183 Overview.................................................................................................................................... 183 News Services and Press Releases.............................................................................................. 183 Newsletter Articles .................................................................................................................... 186 Academic Periodicals covering Lung Disease ............................................................................ 188 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 189 Overview.................................................................................................................................... 189 U.S. Pharmacopeia..................................................................................................................... 189 Commercial Databases ............................................................................................................... 190 Researching Orphan Drugs ....................................................................................................... 191 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 195 Overview.................................................................................................................................... 195 NIH Guidelines.......................................................................................................................... 195 NIH Databases........................................................................................................................... 197 Other Commercial Databases..................................................................................................... 200 APPENDIX B. PATIENT RESOURCES ............................................................................................... 201 Overview.................................................................................................................................... 201

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Patient Guideline Sources.......................................................................................................... 201 Finding Associations.................................................................................................................. 212 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 215 Overview.................................................................................................................................... 215 Preparation................................................................................................................................. 215 Finding a Local Medical Library................................................................................................ 215 Medical Libraries in the U.S. and Canada ................................................................................. 215 ONLINE GLOSSARIES................................................................................................................ 221 Online Dictionary Directories ................................................................................................... 222 LUNG DISEASE DICTIONARY................................................................................................. 223 INDEX .............................................................................................................................................. 305

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with lung disease is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about lung disease, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to lung disease, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on lung disease. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to lung disease, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on lung disease. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON LUNG DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lung disease.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and lung disease, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “lung disease” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Potential Associations Between Chronic Respiratory Disease and Periodontal Disease: Analysis of National Health and Nutrition Examination Survey III Source: Journal of Periodontology. 72(1): 50-56. January 2001. Contact: Available from American Academy of Periodontology. 737 North Michigan Avenue, Suite 800, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Associations between poor oral health and chronic lung disease have recently been reported. This article reports on a study that evaluated these potential associations by analyzing data from the National Health and Nutrition Examination Survey III (NHANES III), which documents the general health and nutritional status of randomly selected United States subjects from 1988 to 1994. This cross sectional, retrospective study of the NHANES III database included a study population of 13,792

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subjects older than 20 years of age, with at least 6 natural teeth. A history of bronchitis or emphysema was recorded from the medical questionnaire, and a dichotomized variable combined those with either chronic bronchitis or emphysema, together considered as chronic obstructive pulmonary disease (COPD). Subject lung function and oral health status were assessed. Analyses adjusted for age, gender, race and ethnicity, education, income, frequency of dental visits, diabetes mellitus, smoking, and alcohol use. The mean age of all subjects was 44.4 years (plus or minus 17.8 years); the mean age of subjects with COPD was 51.2 years and subjects without COPD was 43.9 years. Subjects with a history of COPD had more periodontal attachment loss (a measure of periodontal disease) than subjects without COPD. A trend was noted in that lung function appeared to diminish with increasing periodontal attachment loss. The authors conclude that these findings support recently published reports that suggest an association between periodontal disease and COPD. 4 tables. 46 references. •

Ischemic Hepatitis: Clinical and Laboratory Observations of 34 Patients Source: Journal of Clinical Gastroenterology. 26(3): 183-186. April 1998. Contact: Available from Lippincott-Raven Publishers. P.O. Box 1550, Hagerstown, MD 21741. (800) 638-3030 or (301) 714-2300. Summary: Ischemic hepatitis, a relatively infrequent disorder occurring in 0.16 percent to 0.50 percent of patients admitted to medical intensive care units, often follows episodes of hypotension or acute heart failure. This article reports on a retrospective analysis of 34 patients undertaken to examine the possible contribution of the various baseline characteristics of patients with ischemic hepatitis to the severity of the hepatic (liver) damage. In all patients, liver disease was unexpected, and in some, liver dysfunction dominated the clinical picture. All patients had high serum glutamic pyruvic transaminase (SGPT) and lactic dehydrogenase levels. Most patients had coagulopathy with a prolonged prothrombin time. The most common diagnosis on admission was respiratory distress secondary to various causes. Before the development of hepatic dysfunction, respiratory failure and hypoxemia (low blood levels of oxygen) were observed in 68 percent of the patients, whereas hypotension (low blood pressure) was observed in only 38 percent. More than 90 percent of the patients had three or more associated comorbid conditions. The most frequent of these were left heart failure (88.2 percent), right heart failure (67.6 percent), chronic obstructive lung disease (58.8 percent), and chronic renal failure (55.9 percent). During the acute episode, more than 90 percent of the patients had transient deterioration of their renal function. Hypoglycemia was noted in 11 patients (32.4 percent) and the glucose level was inversely correlated with the SGPT level. Fourteen patients (41.2 percent) died during the 3 month followup period, but none from hepatic injury. None of the clinical or laboratory parameters that were measured predicted mortality. Clearly, ischemic hepatitis is associated with a high risk of death. Characteristic patients are those with multiple underlying systemic diseases and conditions, especially those with left heart failure. The authors stress that results of liver function tests and levels of liver enzymes should be monitored in these patients, particularly when they are admitted for respiratory deterioration and episodes of hypotension. 2 tables. 22 references. (AA).

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Seven-Year Survival Rate After 85 Years: Relation to Alzheimer Disease and Vascular Dementia Source: Archives of Neurology. 55: 1226-1232. September 1998.

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Summary: This article describes an investigation of the relationship between very elderly individuals' survival rate and Alzheimer's disease (AD), vascular dementia, and other mental and physical disorders. Data showed that the 7-year survival rate after age 85 was 34.5 percent higher in women than in men, and that AD and vascular dementia predicted 30.7 percent of deaths in men and 49.7 percent of deaths in women. A regression analysis showed that mortality in men was predicted by the presence of chronic obstructive lung disease, AD, vascular dementia, cancer of the gastrointestinal tract, and skin cancer; in women by vascular dementia, AD, cerebrovascular disorders, congestive heart failure, hypertension, myocardial infarction, and cancer of the gastrointestinal tract. Life expectancy decreased with severity of dementia; survival time in individuals with mild AD did not differ from that in individuals with no dementia. The authors conclude that AD and vascular dementia influence the mortality rate considerably in extreme old age. 2 figures, 3 tables, 52 references. (AA-M). •

Differential Diagnosis of Dementia, Delirium and Depression: Implications for Drug Therapy Source: Drugs and Aging. 5(6): 431-445. December 1994. Summary: This article discusses the differential diagnosis, evaluation, and treatment options for dementia, delirium, and depression. It presents the clinical features and causes of each disorder and the neuropsychological and laboratory tests used in diagnosis. Comprehensive clinical evaluation is necessary because these disorders are not mutually exclusive. Furthermore, physical diagnoses, such as chronic obstructive lung disease, congestive heart failure, stroke, and endocrine disorders are frequently associated with depressive symptoms. Laboratory testing is required to exclude concurrent metabolic, endocrine and infectious disorders, and drug effects. Imaging studies should be obtained selectively in patients with signs and symptoms, such as focal neurological findings and gait disturbances, which are suggestive of structural lesions: stroke, subdural hematoma, normal pressure hydrocephalus, and brain tumors. Appropriate management involving pharmacological and nonpharmacological measures could result in significant improvement in most patients with these syndromes. In delirious patients the underlying illness may be treated concomitantly with the use of psychotropics, if necessary. Although no current medications have been shown to have a significant effect on the functional status of patients with the two most common causes of dementia, Alzheimer's disease (AD) and multi-infarct dementia, the management of concomitant illness in these patients may result in improved function for as long as a year. Tacrine (Cognex) improves cognitive function slightly in selected patients with AD over short periods. Finally, the treatment of depression with medications or electroconvulsive therapy may result in significant reductions in mortality and morbidity. 4 tables, 43 references. (AA-M).

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Pedometer-determined Ambulatory Activity in Individuals with Type 2 Diabetes Source: Diabetes Research and Clinical Practice. 55(3): 191-199. 2002. Summary: This article reports on a cross sectional study on pedometer-determined ambulatory activity, defined as steps per day, in 160 individuals (98 males, 62 females; mean age 52.4 years plus or minus 5.3 years, body mass index 32.3 plus or minus 5.7) with type 2 diabetes. Participants took 6,662 steps (plus or minus 3,077) per day, less than that reported in samples with diabetes and more than that reported for samples living with more restrictive chronic conditions including claudication, joint replacement, chronic obstructive lung disease (COLD), and chronic heart failure. Steps per day and BMI were inversely and significantly correlated. Further, there was a significant

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difference between BMI categories (from normal weight to obesity class III) with regard to steps per day. The authors note that objective quantification of ambulatory activity via simple and inexpensive pedometers permits researchers and practitioners to easily screen for level of activity along a continuum. 1 figure. 5 tables. 33 references. •

Epidemiology of Surgically Managed Pelvic Organ Prolapse and Urinary Incontinence Source: Obstetrics and Gynecology. 89(4): 501-506. April 1997. Summary: This article reports on a study to determine the incidence of surgically managed pelvic organ prolapse and urinary incontinence (UI) in a population-based cohort, and to describe their clinical characteristics. The retrospective cohort included all patients undergoing surgical treatment for prolapse and incontinence during 1995; all were members of Kaiser Permanente Northwest, which included 149,554 women aged 20 or older. A standardized data collection form was used to review all inpatient and outpatient charts of the 395 women identified. Variables examined included age, ethnicity, height, weight, vaginal parity, smoking history, medical history, and surgical history, including the preoperative evaluation, procedure performed, and details of all prior procedures. Results showed that the age-specific incidence increased with advancing age. The lifetime risk of undergoing a single operation for prolapse or incontinence by age 80 was 11.1 percent. Most patients were older, postmenopausal, parous, and overweight. Nearly half were current or former smokers, and one-fifth had chronic lung disease. Reoperation was common (29.2 percent of cases), and the time intervals between repeat procedures decreased with each successive repair. The authors call for further epidemiologic research in order to determine the etiology, natural history, and longterm treatment outcomes of these conditions. 1 figure. 8 tables. 21 references. (AA-M).

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Major Complications of Coeliac Disease Source: Clinical Gastroenterology: International Practice and Research. 9(2): 351-369. June 1995. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Summary: This article reviews the major complications of celiac disease. The author notes that it is claimed that adherence to a gluten-free diet returns patients with celiac disease to a normal life expectancy and that they ultimately die from unrelated causes. While this may be true for an individual patient, the mortality rate for all patients with celiac disease is increased above that of the general population. This increased mortality rate is largely from an increased prevalence of malignant disease, particularly malignant lymphoma. The author hypothesizes that this may be partly because a large number of patients have subclinical or silent celiac disease and thus would not realize that they ought to be following a gluten-free diet. The author details the various complications, included malignant lymphoma, other malignancies, chronic ulcerative enteritis, liver disease, lung disease, neurological disorders, and hyposplenism. The author reports on research findings that suggest that enteropathy associated T-cell lymphoma arises in the setting of celiac disease and evolves from reactive intraepithelial lymphocytes through a low-grade lymphocytic neoplasm to a high-grade tumor, which is usually the cause of the presenting symptoms. Most cases of chronic ulcerative enteropathy (ulcerative jejunitis) are probably part of the same disease process. Carcinoma of the pharynx and esophagus, and adenocarcinoma of the small intestine, are increased in frequency in

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patients with celiac disease. The increased risk of carcinoma of the esophagus may be related to vitamin A deficiency. Splenic atrophy occurs frequently in patients with celiac disease and is related to the severity of the disease and degree of dietary control. 7 figures. 75 references. •

Suspected Kidney Disease: Putting Urinalysis Clues Into Context, Part 1 Source: Consultant. 41(13): 1749-1750, 1752-1753, 1756-1757. November, 2001. Contact: Available from Cliggott Publishing Company. 330 Boston Post Road, Darien, CT 06820-4027. (203) 661-0600. Summary: This first article in a two part series uses a case based approach to illustrate typical urinalysis results found in common renal diseases. The authors show how these results can be integrated with findings from the history, physical examination, and other laboratory studies to arrive at a reliable diagnosis and to guide treatment. Typical urinalysis (urine testing) results in patients with nephritic disease are proteinuria greater than 2 to 3 grams per 24 hours, blood detected by dipstick and microscopic examination, and red blood cell (RBC) casts in the urine. Other findings may include cryoglobulinemia (both polyclonal and monoclonal), low complement levels, and gross hematuria. Characteristic urine findings in patients with nephrotic disease are proteinuria greater than 4 grams per 24 hours, no blood or less than is seen in nephritic disease, and casts without RBCs. Nephrotic disease is also associated with edema, a low albumin level, and a high cholesterol level. An antineutrophilic cystoplasmic antibody (ANCA) assay is useful in determining the underlying cause of rapidly progressive glomerulonephritis. For example, in a patient with azotemia and cavitary lung disease, the presence of cytoplasmic ANCA suggests Wegener granulomatosis. 3 figures. 4 tables. 10 references.

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Methotrexate Pulmonary Toxicity Source: Rheumatic Disease Clinics of North America. 23(4):917-937; November 1997. Summary: This journal article for health professionals focuses on methotrexate (MTX) pulmonary toxicity, which is a well-recognized complication of MTX treatment of rheumatic disease. The article reviews the different types of MTX-induced pulmonary diseases, including acute interstitial pneumonitis, interstitial fibrosis, noncardiogenic pulmonary edema, pleuritis and pleural effusions, and pulmonary nodules. It describes the clinical features of MTX-induced pulmonary disease, including its symptoms; physical signs; and laboratory, radiographic, and pathologic findings. The article reports on the proposed criteria for diagnosing MTX-induced lung disease. It identifies the risk factors for MTX-induced lung disease, including MTX dose, duration, and treatment schedules; demographic factors; clinical laboratory parameters; and pre-existing lung disease. In addition, the article suggests an approach for managing MTX-induced pulmonary disease and the rheumatic disease patient who develops new pulmonary symptoms while receiving MTX. It stresses the need for educating all patients receiving MTX about its potential life-threatening drug toxicity. 67 references, 3 figures, and 3 tables. (AA-M).

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Extramuscular Manifestations in Idiopathic Inflammatory Myopathies Source: Current Opinion in Rheumatology. 10(6): 556-561. November 1998. Summary: This journal article provides health professionals with information on the extramuscular manifestations of the major syndromes of chronic idiopathic

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inflammatory myopathy, including cutaneous, pulmonary, and cardiac manifestations; calcinosis; and joint involvement. Dermatological manifestations in dermatomyositis are often so characteristic that they are virtually pathognomonic. Histopathological findings that are typical of dermatomyositis include focal epidermal atrophy, liquefaction of the basal layer, mucin deposition, and a perivascular and dermal infiltration of mononuclear cells and lymphocytes. Therapy for dermatological manifestations of dermatomyositis depends on whether the patient has both skin and muscle involvement or the characteristic rash in the absence of overt muscle disease. In the former case, systemic treatment with agents such as corticosteroids, intravenous gamma globulin, methotrexate, azathioprine, cyclosporine, and hydroxychloroquine is the usual standard of care. In the latter case, treatment appropriate for the severity of disease manifestations would seem the best approach. Calcinosis is frequently seen in children or young adults with dermatomyositis. Therapeutic agents include warfarin, colchicine, bisphosphonates, intralesional corticosteroids, phosphate binding antacids, probenecid, and calcium channel blocking agents. Respiratory complaints can be a prominent and serious feature in people who have inflammatory muscle disease. Pulmonary problems include exertional dyspnea, upper pharyngeal weakness and dysfunction, infections, interstitial lung disease, and aggressive diffuse lung disease. Corticosteroids, immunosuppressives, methotrexate, and intravenous gamma globulin have been used to treat interstitial lung disease. Although clinically symptomatic cardiac involvement in polymyositis and dermatomyositis is uncommon, various abnormalities of structure and function have been described. Joint involvement can occur in both polymyositis and dermatomyositis. This manifestation is characterized by arthralgia or arthritis of the wrists, knees, and small joints of the hands. Although gastrointestinal involvement in dermatomyositis and polymyositis is not usually clinically apparent, dysphagia that can be complicated by aspiration does occur. Abnormalities of gastric emptying have also been documented. 1 table and 52 references. (AA-M). •

What's New in Pathology, Pathophysiology and Conservative Treatment of Benign Esophageal Disorders? Source: Diseases of the Esophagus. 10(2): 149-154. April 1997. Contact: Available from Pearson Professional Ltd. P.O. Box 77, Harlow, Essex CM19 5BQ, England. Phone: 44 0 1279 623 924; Fax: 44 0 1279 639 609. Summary: This review article considers advances in the pathology, pathophysiology, and conservative treatment of benign esophageal disorders. Topics include the investigation of esophageal motility; motility and esophageal disease; gastroesophageal reflux disease (GERD), including its pathophysiology, symptoms, investigation, histology, endoscopy, and medical treatment; Barrett's esophagus; GERD and lung disease; esophageal strictures, foreign bodies, and cancer; esophageal complications of disease, injury or treatment; achalasia; and esophageal varices. The authors summarize recent research in each of these topic areas. Treatment options for GERD include weight reduction and drug therapy (omeprazole, ranitidine, lansoprazole). The authors discuss the esophageal complications of AIDS, notably candidal esophagitis. The mainstay of treatment for achalasia is pneumatic dilatation. 75 references. (AA-M).

Federally Funded Research on Lung Disease The U.S. Government supports a variety of research studies relating to lung disease. These studies are tracked by the Office of Extramural Research at the National Institutes of

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Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to lung disease. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore lung disease. The following is typical of the type of information found when searching the CRISP database for lung disease: •

Project Title: A PROTEOMICS APPROACH IN THE STUDY OF NOVEL COPD MARKERS Principal Investigator & Institution: Djukanovic, Ratko; University of Southampton Highfield Southampton, Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): COPD is a major health problem worldwide, but our level of understanding of its mechanisms, when compared to the other important airway disease, asthma, is relatively poor. COPD is a disease which progresses at a slow rate, which makes it very difficult to study its natural history and the impact of any therapeutic intervention. For all these reasons, it is vitally important to discover biomarkers that are elective for COPD, i.e., they are not general markers of lung inflammation and remodeling, and are prognostic for the rate of clinical deterioration. A number of non-invasive markers have been studied to date; to our knowledge, none of these have fulfilled the above criteria. As with other inflammatory lung diseases, a host of inflammatory and remodeling processes are involved in the pathogenesis of COPD, which render a singlemarker approach unlikely to succeed. We hypothesize that a number of proteins or protein isoforms are differentially expressed in the airway lining fluid in COPD and that these reflect the chronic pathology of COPD, rather than the chronic and acute effects of smoking. We propose to test this hypothesis using a proteomics approach as our primary, unbiased filter, to identify a set of 15 differentially expressed proteins (DEPs) that are present in a group of meticulously characterized subjects with COPD, but not present in those who have no evidence of lung damage despite an equivalent smoking history. Our programme is staged in a way to optimize the use of the state-of-the-art proteomics technology and precious archival samples collected over up to 17 years at the University of Nebraska and more recently in Southampton. Because we believe that patterns (groups) of biomarkers are more strongly related to COPD, we will apply multivariate analyses to identify the DEPs, which will thus become Early Candidate COPD-Selective Biomarkers. We will then develop antibodies against these in order to provide reagents for immunoassays. The latter will be applied to potentially as many as 480 subjects who have COPD, chronic severe asthma, or are healthy smokers or non-smokers. This will allow us to follow a logical sequence of further selection of biomarkers with respect to their selectivity for COPD, presence in early stages of smoke-induced lung damage and their prognostic

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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value in terms of clinical deterioration and decline in lung function. Finally, applying the antibodies to archival lung tissue samples we will be able to localize the COPDselective proteins to the airway and alveoli, adding valuable knowledge to our understanding of COPD mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ACADEMIC TRAINING PROGRAM IN PEDIATRIC PULMONARY DISEASE Principal Investigator & Institution: Abman, Steven H.; Professor, Pulmonary Medicine; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 15-JUL-1994; Project End 30-JUN-2004 Summary: Advances in our understanding and treatment of childhood respiratory disorders have been limited by a lack of insight into basic mechanisms of disease and the development of novel therapeutic strategies. The purpose of this program is to provide rigorous multi-disciplinary training for academically-oriented pediatricians interested in childhood lung diseases. This proposal is a renewal of the NIH Training Program in Pediatric Lung Disease at the University of Colorado School of Medicine, and represents the continuation of a well-established program that has existed since 1988. This current proposal has been expanded to represent the evolution of our training program and to reflect our highly interactive, multi-disciplinary faculty. Strengths of this program include benefits derived from the integration of extensive resources of two collaborating hospitals (The Children's Hospital (TCH) and National Jewish Medical and Research Center (NJMRC)) and five research units at the NJMRC and the UCHSC campus (Developmental Lung Biology Laboratory, Pediatric Heart Lung Center Laboratory, the Perinatal Research Facility, and the Cardiovascular Pulmonary Laboratories). These resources are combined into a versatile training environment for both basic and applied research. Faculty in this program include the PIs of 2 PPGs, 2 SCORs, a Therapeutic Development Center Award in Cystic Fibrosis, an NIH Clinical Research Center Grant, and several individual awards that address basic, applied and clinical research questions in the area of pulmonary biology. Collaborations between laboratory and clinical investigators are a major strength of this proposal, enhancing interactions between scientists and clinicians from diverse backgrounds and encouraging "bench to bedside" approaches to pediatric lung disease. All participants in the training program are full-time academic faculty, and include pediatric pulmonary and critical care physician- investigators, along with several basic (PhD) and other scientists from throughout UCHSC. The most promising individuals with clearly defined academical goals are selected from candidates within our pediatric pulmonary, critical care and neonatology fellowship training programs. After a clinical year of training (funded from other sources), laboratory or clinical research experience is provided under the direct mentorship of a senior investigator. Structured course work in statistics, molecular biology, cell physiology, ethics, and other areas are provided to the trainees. Review of fellows' progress is closely monitored by the head of the training grant, fellowship directors, their laboratory mentor and special advisors to the program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ADENOSINE SIGNALING AND LUNG FIBROSIS Principal Investigator & Institution: Blackburn, Michael R.; Assistant Professor; Biochem and Molecular Biology; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225

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Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Interstitial lung disease leads to more than 30,000 hospitalizations and 5,000 deaths yearly in the United States. A subset of interstitial lung disease known as idiopathic pulmonary fibrosis (IPF) is particularly devastating. Basic research into the mechanisms that govern this disease are needed to help develop novel therapies for its treatment. The focus of this proposal is to characterize a novel model of lung fibrosis that implicates adenosine signaling in this disease. Adenosine is a signaling nucleoside that engages specific adenosine receptors on the surface of target cells to elicit a vast array of cellular responses. Elevated adenosine levels are thought to play a role in inflammatory lung diseases such as asthma and COPD; however, the involvement of this signaling pathway in IPF has not been examined. We have recently generated a line of mice that contain low levels of the enzyme adenosine deaminase (ADA), which is responsible for controlling the levels of adenosine in tissues and cells. These partially ADA-deficient mice exhibit progressive elevations in lung adenosine concentrations and in turn die from severe interstitial lung disease characterized by the histologic, immunologic and inflammatory hallmarks of IPF. This suggests that chronic elevations in adenosine may access signaling pathways that lead to the inflammation and damage seen IPF. Therefore, the hypothesis being tested is that chronic elevations in adenosine contribute to lung inflammation and fibrosis. Four specific aims are designed to address this hypothesis: Aim 1, Characterize the lung fibrosis seen in partially ADAdeficient mice and determine the dependence of this phenotype on elevations in adenosine. Aim 2, Characterize the pattern of adenosine receptor expression in the lungs of partially ADA-deficient mice and determine their function using genetic and pharmacologic approaches. Aim 3, Examine adenosine-signaling pathways in an established model of lung fibrosis. and Aim 4, Examine the efficacy of novel therapies on lung fibrosis. Knowledge obtained from these experiments will improve our understanding of the cellular signaling pathways involved in interstitial lung diseases such IPF, which will aid the development of adenosine-based therapeutics for the treatment of this deadly disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AIRWAY EPITHELIAL CELL CHLORIDE CHANNELS Principal Investigator & Institution: Wine, Jeffrey J.; Psychology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 30-JUN-2001 Summary: (Taken directly from the application) The central hypothesis of our research is that the loss of CFTR-mediated, apical membrane chloride conductance is the fundamental physiological defect that leads to airways disease in cystic fibrosis. The general goal of our research is to confirm or negate that hypothesis. The most puzzling aspect of CF lung disease is how it begins. A direct attack on that question is not possible at present because no adequate animal model of human CF lung disease exists. Elsewhere, we propose a strategy to produce such a model. Here, we propose experiments that are feasible with available model tissues and that deal with two of most basic questions in CF research: how does CFTR operate as an ion channel, and what other chloride ion channels are important players in the lung. The proposal has 4 specific aims. Aim 1 is to understand the mechanism and functional significance of natural "lock-open" kinetics that we have discovered in CFTR channels of human airway cells. Aim 2 is to test the hypothesis that some mutations in CFTR lead to disease in whole or in part because they interfere with CFTR's ability to display locked-open kinetics. Aim 3 is to identify other chloride channels and determine their role in airway

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cell function. Aim 4 is to study changes in channel populations that occur with epithelial cell polarization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERATION OF PULMONARY IMMUNE SYSTEM BY DIESEL PARTICLE Principal Investigator & Institution: Ma, Joseph K.; Professor; Basic Pharmaceutical Sciences; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: The objective of the proposed research is to investigate the effects of diesel exhaust particles (DEP) on the development of chronic lung diseases in animal models. Preliminary studies in rates showed that DEP induced pulmonary inflammation and inhibited alveolar macrophage (AM) host defense function. Specifically, DEP inhibited AM secretion of cytokines in response to endotoxin stimulation, and resulted din altered thiol (cysteine and glutathione) levels that are known to regulate T lymphocyte function. These results indicate that DEP can change the susceptibility of the lung to bacterial infection and allergic sensitization. The proposed research will study the mechanism of the DEP effects indicated in the preliminary studies based on the following hypotheses. (1) DEP impair cell-mediated immunity in the lung, which can be illustrated by measuring the weakened host defense against the obligate intercellular pathogen, listeria monocytogens; (2) DEP augment antigen- elicited humoral immune responses, increasing the likelihood and severity of sensitization, and worsening the clinical outcome. Theses hypotheses will be tested using a L. Monocytogens rate model for cellmediated immunity and the Brown-Norway rate (BNR) model for allergic sensitization. Exposure of rates to DEP will be carried out by inhalation. The DEP effects will be assessed with an acute and a sub-chronic exposure protocol, via the following studies: (a) to establish the effects of inhalation DEP exposure on pulmonary inflammation; (b) to characterize the pulmonary immune-inflammatory responses to L. Monocytogens and the effect of DEP on the host defense mechanism; to assess the integrative effect of DEP and antigen sensitization on airway hyper reactivity; and (d) to establish the DEP effects on T lymphocyte function, AM- regulated thiol levels and cytokine productions in the BNR model. In year 1, studies will be focused on the effects of DEP on Listeria infection and allergic sensitization via acute DEP exposure. A sub-chronic exposure protocol will be established. In years 2 and 3, studies will be focused on the interactive effects of the disease state with sub-chronic DEP exposure and the mechanism(s) by which DEP alter pulmonary immunity. By using the two disease models, this research will characterize the cellular (TH1) and humoral (TH2) responses to DEP exposure, and test the hypothesis that DEP suppress the cellular buy enhance humoral immune responses by altering AM-regulated thiol homeostasis in the lung. The strengths of this proposal are 1) the strong and robust assumptions underlying the hypotheses, 2) the extent of preliminary data available, 3) the investigator's experience in these methods and preparations, and 4) the inhalation system, which is proven. The weaknesses of this proposal are 1) its complexity and the complicated logistics required for execution, and 2) uncertainties in extrapolation to human exposure and expression of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ASBESTOS AND NO2 IN ENVIRONMENTAL LUNG DISEASE Principal Investigator & Institution: Heintz, Nicholas H.; Professor; Pathology; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405

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Timing: Fiscal Year 2001; Project Start 15-AUG-1998; Project End 31-JUL-2002 Summary: Exposure of the human lung to environmental particulates and gases contributes to a variety of diseases, including pulmonary fibrosis and cancer. Previous work in our research group has shown that asbestos, reactive oxygen species (ROS), and reactive nitrogen species (RNS) trigger specific cell signaling pathways in target cells of the lung, leading to activation of transcription factors such as AP-1 and NF-KB. These and other transcription factors are involved in cellular decisions leading to phenotypic changes involved in the initiation of lung disease. To extend our understanding of cellular responses to mixtures of chemical and physical agents, we propose to study the effects of chrysotile asbestos and nitrogen dioxide (NO2), either alone or together, on three endpoints of exposure: cell survival, cell cycle progression, and apoptosis. First, we will characterize the responses of rat lung epithelial (RLE) cells and rat lung fibroblasts (RLF) to asbestos and/or N02, in regard to the activation of the transcription factors AP-1, NF-KB, and E2F and their downstream target genes. Activation of cyclindependent kinases (CDKs), metabolism of their protein inhibitors (i.e., CKIs p15, pl6, pl8, p2l, and p27),and phosphorylation of retinoblastoma family proteins (pRB and pl3O) will be studied as regulators of cell cycle progression. Cell imaging techniques, flow cytometry and activation of proteases will be used to measure apoptotic responses. Transient expression of dominantnegative regulatory molecules will be used to dissect mechanisms of exposure responses. For physiological relevance, results from experiments using models for cell cycle control and apoptosis in Vitro will be verified by inhalation studies using mice. Finally, to test the contributions of specific proteins such as p53, CKIS, and other candidate cell cycle regulators in cell cycle activation and/or apoptosis by asbestos and N02, inhalation studies will be performed in transgenic mice lacking specific genes of interest. Dissection of the role of cell cycle and survival regulators in proliferative and apoptotic responses to the combined effects of asbestos and N02 may lead to new biomarkers for exposure of the human lung to chemical mixtures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ASTHMA CANDIDATE GENES IN ALPHA 1-ANTITRYPSIN DEFICIENCY Principal Investigator & Institution: Demeo, Dawn L.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a disease of tremendous public health concern. Cigarette smoking is the major environmental risk for disease, but the development of airflow obstruction is variable amongst smokers. COPD is likely a genetically complex disease, but alpha 1-antitrypsin (AAT) deficiency is the only known genetic risk factor for COPD. Variability in lung function decline also exists among individuals with severe AAT deficiency (genotype PI ZZ), suggesting the presence of other genetic factors relevant to disease development and progression. A subset of individuals with COPD will also have manifestations of asthma. We hypothesize that genes associated with asthma and asthma-related phenotypes represent modifying factors for the expression of COPD in individuals with severe AAT deficiency. Through the funded NIH project "Genetic Modifiers of Alpha 1Antitrypsin Deficiency" (RO1 HL 68926), 400 families are being collected that include at least two adult PI ZZ siblings. We propose to investigate asthma phenotypes and asthma candidate gene polymorphisms in these families, using a candidate gene approach and family-based association tests for analysis, to pursue three distinct

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hypotheses, 1). We hypothesize that asthma phenotypes are common in PI ZZ AAT deficient individuals, and may be modified by age, sex, and level of lung function. 2) We hypothesize that asthma candidate gene polymorphisms are associated with asthma phenotypes in PI ZZ individuals. 3) We hypothesize that asthma candidate gene polymorphisms are associated with COPD phenotypes in PI ZZ individuals. Familybased association analysis of asthma candidate genes in a population enriched to develop COPD from a major gene effect will be complementary to the ongoing project that uses genome scanning and linkage analysis to identify modifier genes for COPD in this population. Understanding modifying factors for lung disease in individuals with AAT deficiency will potentially have important prognostic and therapeutic impact. The identification of modifying factors of COPD in AAT deficiency may have significant public health relevance to COPD patients without AAT deficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR AND MOLECULAR MECHANISMS OF LUNG DISEASE Principal Investigator & Institution: Stanton, Bruce A.; Professor; Physiology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The goals of this application are to increase the number of investigators in New Hampshire who are competitive in securing NIH funding, and to establish a Lung Biology Center that will be nationally recognized and free standing in five years. Based on a core of existing collaborative and multidisciplinary faculty at Dartmouth and Keene State College (KSC) along with other investigators in the State, COBRE funding will provide resources to develop junior faculty and infrastructure necessary to attain Center status. Faculty growth and development will be facilitated in five ways: 1) recruitment of three tenure-track faculty: two at Dartmouth, and one at Keene State College; 2) mentored development of four junior investigators already at Dartmouth, and one already at Keene State College; 3) linkage between Dartmouth, Keene State College and investigators in the State who provide expertise not available at Dartmouth; and 5) synergistic scientific collaboration through the research projects and associated administrative and proteomic cores. Under the leadership of Dr. Stanton, the current Director of the Lung Biology Program at Dartmouth, together with substantial institutional commitments, we are confident that the existing base of investigators will expand and mature with COBRE funding to an established Center, comprised of faculty who will be more competitive in obtaining NIH funding, and thereby enhance the research grant portfolio of the State. The five research projects exhibit a multidisciplinary approach characteristic of a Center and are connected by the common themes of lung biology and disease including cystic fibrosis (CF), cancer and lung injury as well as proteomics. Project 1 will examine biofilm formation in the CF lung. Project 2 will study ?F508-CFTR trafficking. Project 3 examines the structural basis of the CFTR-PDZ protein interactions that regulate the function and trafficking of CFTR. The ultimate goals of Projects 1-3, which are complementary in approach, are to elucidate the cellular mechanisms of lung disease in CF. In Project 4 the major goal is to identify biomarkers that can be used to determine causal relationships between exposure to airborne pollutants and increased incidence of cancer, obstructive airway disease and asthma. The goal of Project 5 is to use a multilevel approach using Geographic Information Systems and case-reference methods to study the environmental epidemiology of lung cancer. Together these projects will contribute to the growth of our Program and to a better understanding of the cellular and molecular

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mechanisms that underlie lung disease. The long-term goal of our Program is to conduct translational studies to develop new treatments and cures for lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINE AND CHEMOKINE RECEPTORS IN IPF Principal Investigator & Institution: Hogaboam, Cory M.; Associate Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 26-DEC-2001; Project End 30-NOV-2006 Summary: (Applicant's Abstract) Interstitial lung disease (Il-D) encompasses a group of pulmonary inflammatory disorders that are characterized by excessive tissue injury and progressive fibrosis. Clinical and laboratory evidence suggest that ILD is a consequence of a poorly regulated pulmonary inflammatory process because of the persistence of one or several inflammatory signals. Recent experimental data suggest that the lung fibroblast is not a bystander during chronic inflammatory responses in the lung, rather this structural cell has a very specialized role in the recruitment and regulation of immune cells that infiltrate the interstitial space. The role of the fibroblast during ILD has expanded because of the recent recognition that this cell markedly increases the generation of chemotactic proteins (chemokines) and directly responds to these factors through the expression of high-specialized chemokine receptors. Chemokines affect both the proliferation and synthetic capacity of pulmonary fibroblasts. Although increased chemokine levels during ILD have been reported, little is known about changes in the chemokine and chemokine receptor expression in the fibroblast during ILD, nor is it known whether the temporal pattern of expression of chemokine receptors by these cells may aid in differentiating the various pathologically distinct types of ILD or success of ILD treatment. Thus, the overall aim of this proposal is to characterize the pattern of chemokine and chemokine receptor expression associated with non-specific interstitial pneumonia (NSIP)-cellular, NSIP-fibrotic, usual interstitial pneumonia (UIP)discordent, and UIP-cordent in open lung biopsies (OLB), fibrotic foci and cultured fibroblasts from OLB and transbronchial biopsies. The following specific aims will be addressed using powerful new techniques including TAQMAN quantitative polymerase chain reaction (PCR) and laser capture microscopy: 1) to characterize the chemokine and chemolcine receptor profile in OLB from patients at the time of ILD diagnosis, and specifically identify the chemokine receptor profile in fibrotic foci from histological samples. 2) to characterize the chemokine and chemokine receptor profile in fibroblasts cultured from open lung biopsies at the time of ILD diagnosis. 3) to examine changes in the chemokine and chemokine receptor profile in cultured transbronchial biopsy fibroblasts at defined intervals after initial ILD diagnosis and during a defined ILD treatment regimen. Taken together, these studies entail an examination of the expression of chemokines and their receptors in OLB, fibrotic foci and cultured lung fibroblasts at the time of diagnosis and during ILD treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMOKINE BLOCKADE TO PRESERVE LUNG DEVELOPMENT Principal Investigator & Institution: Auten, Richard L.; Pediatrics; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Chronic lung disease in prematurity (CLD) may affect as many as 50% of very low birthweight newborns. CLD confers added risk for abnormal

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neurodevelopmental outcome. Inflammation in response to adequate antioxidant defenses in premature newborns is central to the pathophysiology of lung injury leading to CLD. Present therapy includes glucocorticoids which may adversely affect lung, somatic and central nervous system development.,. Targeted immunotherapy blocking early inflammatory-induced lung injury may prevent the development of CLD and avoid adverse steroid effects. Our hypothesis is that blocking leukocyte influx and/of function will prevent chronic lung disease in the hyperoxia-exposed rodent model. The proposed studies will use hyperoxia-exposed newborn rodents to study the mechanisms of inflammatory effects on lung development in response to serve oxidant stress, as a model of CLD. Neutrophil and macrophage influx/function will be modified by using specific anti- chemokine antibodies and chemokine receptor antagonists. The contribution of key neutrophil functions will e studied in gene knockout mice lacking these functions. Aim 1 will determine which aspect of neutrophil and/or macrophage influx/function contributes most to biochemical oxidant stress in newborn lung during initiation of hyperoxia-induced lung injury. Aim 1 will determine which aspect of neutrophil and/or macrophage influx/function contributes most to biochemical oxidant stress in newborn lung during initiation of hyperoxia-induced lung injury. Aim 2 will determine the specific contributions of leukocyte influx/function to DNA damage, growth arrest, and pathologic apoptosis, which contribute to abnormal alveolar development. Aim 3 will determine whether blockade of leukocyte function can safely preserve normal alveolar development during recovery from severe oxidant stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOKINES IN LUNG DISEASE OF HIV1 TRANSGENIC MICE Principal Investigator & Institution: Jolicoeur, Paul; Professor; Clinical Research Institute of Montreal 110 Pine Ave W Montreal, Timing: Fiscal Year 2001; Project Start 07-JUL-1999; Project End 30-JUN-2004 Summary: The long term objective of the research proposal is to study the role of chemokines and their receptors in the pathogenesis of lymphocytic interstitial pneumonitis which develop in transgenic mice expressing some of the HIV-1 genes in specific immune cells (immature CD4+CD8+ T cells, mature CD4+ T cells and cells of the macrophage/dendritic lineage. Our central hypothesis is that this lung disease is immune-mediated and is driven by the recruitment of immune cells in the lung through the action of specific chemokines. In humans infected with HIV-1 and having lymphocytic interstitial pneumonitis, the main population of immune cells found in the lung are the CD8+ T cells. Because the lung lesions of these Tg mice are associated with many other phenotypes very similar to those found in humans infected with HIV-1, we postulate that this model of lung disease is relevant to the lymphocytic interstitial pneumonitis associated with HIV-1 in humans, especially in children. To understand the pathogenesis of this lung disease, we intend: 1- To identify and quantitate the immune cells in the lung. 2- To determine whether these mice exhibit a specific lung microenvironment favoring homing of specific immune cells. 3- To identify the chemokines produced in the lung of these Tg mice. 4- To determine whether blocking or deleting specific chemokines or their receptors and overexpressing some chemokine receptors alter the development of lymphocytic interstitial pneumonitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHRONIC LUNG INJURY AFTER PREMATURE BIRTH Principal Investigator & Institution: Albertine, Kurt H.; Professor of Pediatrics; Pediatrics; University of Utah 200 S University St Salt Lake City, Ut 84112

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Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from the Investigator's Abstract): Bronchopulmonary dysplasia is a complication of prolonged mechanical ventilation after premature birth. To study the pathophysiology of this disease, the investigator has developed an animal model of BPD, following premature delivery of lambs, and 3 weeks of mechanical ventilation. Utilizing this model, physiologic, biochemical, histologic, and molecular techniques will be used to determine (1) if incomplete lung development is essential for the vascular and structural abnormalities of the pulmonary circulation that occur in chronic lung disease, (2) if inhaled nitric oxide will enhance the NO-cGMP cascade and facilitate postnatal regression of vascular smooth muscle in these lambs, and (3) if decreased availability of L-arginine and/or increased activity of cGMP-specific PDE contributes to the sustained elevation of PVR and the abnormal postnatal regression of vascular smooth muscle in these premature lambs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLARA CELL SECRETORY PROTEIN IN LUNG INFLAMMATION Principal Investigator & Institution: Corry, David B.; Assistant Professor of Medicine; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The long- term objectives of this laboratory are to elucidate the immunopathologic basis of airway obstruction in a murine model of asthma. This proposal will investigate the role the epithelium plays in allergic lung inflammation and focus specifically on an epithelium- derived immunoregulatory molecule, Clara cell secretory protein (CCSP), that potentially limits deleterious allergic inflammation of the airway. Work from this laboratory has identified proteases derived from fungi and pollen as critical regulators of T helper activation and allergic inflammation. The dominant role played by proteases raises the intriguing possibility that the lung immune system has evolved mechanisms that limit tissue injury in the setting of allergic inflammation. Clara cells are non- ciliated respiratory epithelial cells that secrete one of the most abundant proteins contained in the respiratory lining fluid, CCSP. Although the biological functions of CCSP remain unclear, it is an antiprotease potentially capable of neutralizing exogenous proteases implicated in allergic airway disease. CCSP may also regulate adaptive immune responses of the airway by influencing epithelium-derived factors necessary for growth and survival of T and B cells. Studies from this laboratory provide preliminary evidence that CCSP downregulates airway Th2 responses provoked by exogenous proteases. Thus, CCSP is immunosuppressive with regard to allergic lung inflammation but its precise mechanisms of action remain uncertain. Aim 1 of this proposal will define the allergic settings relevant to CCSP- dependent regulation. We will investigate whether the potency of both protease- containing and protease- deficient (ovalbumin/alum) allergens is inhibited by CCSP in vivo. The role of CCSP will be evaluated using mice overexpressing CCSP in the airway and CCSP-deficient mice. In part based on the results of Aim 1, we will dissect in Aim 2 the major mechanism by which CCSP attenuates allergic inflammation. We will focus specifically on T cell-dependent effects and explore, with and without CCSP, T helper effector differentiation in vitro and in vivo, Th2 homing to lung and Th2 activation and cytokine production in vitro. Where effects are observed, we will correlate immunosuppressive activities with the antiprotease potential of CCSP. Finally, we will explore the potential of CCSP in the prevention and amelioration of allergic lung disease. Mice will be challenged intranasally with recombinant CCSP during immune induction with protease-

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containing allergens and following established allergic lung inflammation to evaluate these two endpoints. Efficacy of CCSP will be compared to a specific protease inhibitor, streptomyces subtilisin inhibitor (SSI). Together, these data will elucidate an epitheliumdependent immunomodulatory mechanism of the lung mediated through CCSP, and potentially identify novel means for the therapy of allergic lung disorders such as asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLARA CELLS, THEIR SECRETIONS IN LUNG IMMUNOREGULATION Principal Investigator & Institution: Stripp, Barry R.; Associate Professor; Environ & Occupational Health; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Even though cytokine production by cells of the immune system can significantly impact epithelial cell function, little is known of reciprocal roles for epithelial cells in regulation of the immune system. This is a significant issue when trying to understand the complex series of events that lead to deteriorating lung function among individuals with chronic inflammatory and/or immunological lung diseases such as COPD and asthma. There is a growing recognition that the conducting airway epithelium is dynamic in its function and that chronic lung disease results in predictable changes to epithelial cells. Among these changes are alterations in nonciliated airway epithelial cell function, for which reduced abundance of Clara cell secretory protein (CCSP) serves as a biomarker. Whether changes to Clara cells are a cause or a nonciliated airway epithelial cells contribute to exacerbation of lung disease and a continuing decline in lung function. Our recent studies in CCSP null mice (CCSP-/-) demonstrate that Clara cells fulfill important roles in defense against environmental agents in addition to serving critical immunoregulatory functions. Central to this proposal is the observation that CCSP-/- mice have elevated local production of IgA. Moreover, expression of IgA is dramatically up regulated following in vivo endotoxin exposure of CCSP-/- but not wild type mice, demonstrating fundamental differences in B-cell responsiveness with CCSP deficiency. We hypothesize that CCSP functions to suppress the immune system through either directly or indirectly regulating local B-cell function, and that these changes in B-cell function impact innate mucosal defense. If correct, changes in Clara cell function may lead to hyperstimulation of the local immune response which, although beneficial with respect to the acute clearance of colonizing microorganisms, could exacerbate airway disease and dysfunction. Aims will address four specific aspects of altered lung function that accompanies CCSP deficiency: 1) does CCSP deficiency result in altered innate and/or adaptive immunity, 2) are changes in lung immunoregulation and innate defense directly related to loss of CCSP, 3) are differences in innate defense with CCSP deficiency directly related to altered B-and/or T-cell function, and 4) which cell types are most sensitive to CCSP-dependent alterations in endotoxin signaling. By addressing these aims we will define mechanisms by which CCSP deficiency leads to altered immunoregulation within the lung. This knowledge may help in the development of strategies to block inappropriate immunological responses that lead to deteriorating lung function among individuals with chronic lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLLABORATIVE PROGRAM IN BPD Principal Investigator & Institution: Coalson, Jacqueline J.; Professor of Pathology; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2001; Project Start 20-JUL-1994; Project End 31-MAY-2004 Summary: The overall goal of this cooperative research program is to develop a multiinstitutional research effort to address the mechanisms of postnatal lung pathobiology that lead to chronic lung disease and to provide a unique resource center of prematurely delivered baboons with induced bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD) to outstanding investigators from multiple institutions dedicated to sharing collaborative protocols and tissue specimens. In recent years, the original form of BPD described in the 1960's has become less common due to improvements in oxygenation and ventilatory strategies and the use of postnatal exogenous surfactant, and has been replaced by a less severe from of disease primarily in extremely small immature infants, called chronic lung disease of infancy (CLD). The baboon models of BPD and CLD are unique in the world; they develop disease that is very similar, if not identical, of human disease but in a controlled environment. The Southwest Foundation for Biomedical Research and the University of Texas Health Science Center at San Antonio have the breeding colony and the scientific personnel to support the proposed BPD Resource Core. The specific aims of the BPD Resource Core are: 1) To breed baboons to produce pregnancies of known gestational ages, and to delivery by caesarian section 100 timed pregnancies per year, to provide the premature infants that will be shared by multiple investigators. 2) To maintain these premature infant baboons in a neonatal intensive care environment for short periods of up to 14 days, utilizing several well-defined treatment protocols, and long-term outcomes in 1 to 2 month and 42 week survivors, the latter the baboon equivalent of a 2 year old human infant in whom alveolarization should be complete. 3) To provide tissue specimens taken at the time of delivery, during the animal's clinical course, and at necropsy in as ideal and timely a manner as possible, and tailored to each investigator's needs. 4) To provide a Data Management Core for animal information retrieval. This U-10 program brings together the enthusiasm and competence of established investigators with varying backgrounds and expertise who are committed to examining the various aspects of lung development and how, when interrupted, the fetus adapts to the extrauterine environment. It allows, at a national level, a continuing influx of outstanding scientists to address the major deficiencies in our knowledge concerning BPD/CLD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPLEMENT IN ALLERGIC LUNG DISEASE Principal Investigator & Institution: Wetsel, Rick A.; Professor; None; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 10-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The objective of this research proposal is to delineate the overall contribution and potential mechanisms that complement utilizes to mediate the pathogenesis of allergic lung disease. The specific aims of this proposal are driven by the central hypothesis that complement activation products regulate key features of allergen-induced airway disease, including airway hyperresponsiveness (AHR) and acute airway inflammation. The results of this proposal will facilitate the evaluation of complement as a possible therapeutic target in the treatment of asthma. An allergeninduced model of pulmonary allergy in mice with specific complement deficiencies will

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be used to identify the complement pathways, activation fragments, and receptors that are potentially important in mediating the pathogenesis of allergic lung disease. The complement-deficient animals that are subjected to the model will be examined for attenuation of pathological and physiological hallmarks of asthma, including AHR, airway mucus hypersecretion, elevated IgE levels and lung eosinophils. The Th2 cytokines (IL-4, IL-5, IL-13) that have been proposed to play a pivotal role in asthma will also be examined for altered expression. In addition to the murine experimental allergic model, studies with human T-cells as well as other leukocytes isolated from patients with allergic lung disease will be used to examine potentially altered complement mediated cellular responses in asthma. Four specific aims are proposed to accomplish the research goals: 1) to examine the importance of each complement activation pathway in eliciting the asthma associated responses in an allergen-induced model of pulmonary allergy, 2) to determine how the complement anaphylatoxin receptors (C3aR and C5aR) affect the asthma associated responses in an allergen-induced model of pulmonary allergy, 3) to determine how the fifth complement component (C5) affects the asthma associated responses in an allergen-induced mouse model of pulmonary allergy, and 4) to determine the biological effects of the complement anaphylatoxins (C3a and C5a) in regulating T-cell mediated responses in asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE SURVEILLANCE OF OCCUPATIIONAL HEALTH IN NEW YORK Principal Investigator & Institution: Gelberg, Kitty H.; Bureau of Occupational Health 547 River St Troy, Ny 12180 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: New York, with the assistance of the SENSOR and ABLES programs, has established a structure for occupational disease surveillance and follow-up in New York State. Provisions of the New York State (NYS) Public Health Law mandate the reporting of a number of occupational conditions in NYS. Since 1981, the New York State Department of Health, Bureau of Occupational Health (BOH) has operated a Heavy Metals Registry for the reporting of cases of lead, mercury, arsenic, and cadmium poisoning, and an Occupational Lung Disease Registry for the reporting of cases of work related lung disease. Since 1991, BOH has operated a Pesticide Poisoning Registry and receives reports from healthcare providers of suspected pesticide poisonings. While all of these registries are operational, the extent to which there is active surveillance, with aggressive case finding, ascertainment and follow-up, varies. There are a number of reasons for this variability, including differences in how the diseases are diagnosed and the different reporting sources for the various registries. Additional federal resources will permit us to build upon existing reporting laws and infrastructure and expand current surveillance efforts to help us achieve the NIOSH standards for a model core surveillance system for a range of significant occupational conditions. We propose to conduct general surveillance of existing databases available to the Department of Health such as death certificates and hospital discharge data to assist with documenting the magnitude of occupational injuries and illnesses in New York, and to identify trends and industries occupations at elevated risk. Focus will be primarily upon upgrading our Occupational Lung Disease Registry; however, we will also focus more attention on conducting educational outreach for all of our registries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--CLINICAL Principal Investigator & Institution: Wert, Susan E.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract) Despite recent advances in diagnosis and therapy, respiratory disease remains a major cause of morbidity and mortality in neonates and children. The specific etiologies for lung disease in this population are frequently unknown. The Clinical Core will serve as a resource for the individual program components by collecting and analyzing clinical samples pertaining to a variety of neonatal and adult pulmonary diseases, in which abnormalities of lung development and growth, surfactant function and metabolism, and/or remodeling after injury are suspected. The overall goal of these studies will be to characterize and identify mechanisms that cause idiopathic lung disease and developmental abnormalities. Dr. Lawrence Nogee, Johns Hopkins University School of Medicine, will perform genetic analyses for mutations in lung-specific genes, such as the surfactant proteins, the GMCSF Bc receptor, and TTF-1. Analysis for protein expression in frozen lung tissue, BALF, or tracheal aspirates will be performed by Dr. Jeffrey Whitsett; phospholipid analysis and surfactant function by Dr. Machiko Ikegami; and immunohistochemistry by Dr. Susan Wert, in conjunction with the Morphology Core. Analytical results will be entered into a computerized database for future reference and data analysis. As the Clinical Core identifies novel mutations in lung-specific genes, they will be tested for their capacity to cause lung disease, to disrupt surfactant function and/or metabolism, or to induce pulmonary malformations. Testing of selected mutations in vitro or in transgenic mouse models will be done in the context of each of the individual program components. These studies should enhance our understanding, of pulmonary development and pediatric lung disease, leading to the development of new treatment strategies for respiratory disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--INHALATION TOXICOLOGY Principal Investigator & Institution: Thorne, Peter S.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 29-SEP-1990; Project End 31-MAR-2006 Summary: The Inhalation Toxicology Facility (ITF) consists of 6,000 square feet of contiguous laboratories and offices located in the northwest quadrant of the Institute of Rural and Environmental Health. It is secured space, with no thoroughfare, which is divided into two sections: a laboratory area and an office suite area, each with separate ventilation. This facility is the only laboratory with bona fide inhalation toxicology capabilities at the University of Iowa. A full array of inhalation toxicology, aerosol science, and bioaerosol assay services are rendered to the Center. The primary goal of the ITF is to provide facilities and expertise for EHSRC investigators with peerreviewed, funded projects and those funded through the pilot grant program to enhance the productivity and quality of their environmental health research. The facility provides assistance for new investigative efforts in pulmonary biology, inhalation toxicology, and aerosol science. This facility is designed to assist in testing hypotheses in the following areas: pulmonary biology of environmental lung disease, development and prevention of environmental lung disease, and physicochemical properties and behavior of bioaerosols, aeroallergens, and other airborne toxicants. The facility is equipped for generating and quantifying a variety of aerosols, gases, and vapors for

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exposure by whole-body or nose-only inhalation exposure routes to experimental animals in short-term and long-term exposure protocols. The facility includes a wide range of equipment for exposure, aerosol generation, aerosol monitoring and sampling, pulmonary function monitoring, and necropsy analytical equipment. Eight specific aims are outlined for this facility: 1. Provide consultation and services to Center investigators interested in using animal models for environmental health research; 2. Perform acute, subacute, and sub-chronic inhalation exposures (and sham exposures) on groups of rodents, with rigidly controlled gases, vapors, aerosols, or combined exposures using nose-only or whole-body exposure systems; 3. Establish animal biomarkers of exposure or biomarkers of effect to identify early biologic responses, low-dose functional changes, and susceptibility or host resistence factors; 4. Expand the capability for measurement of sensitive physiologic end points; 5. Develop innovative animal models for investigating or identifying potential causal agents of disease, for developing novel inhalation therapies, or for studying the behavior of aerosols in vivo; 6. Develop improved aerosol and bioaerosol sampling and analysis methodology using new analysis systems; 7. Develop novel bioaerosol identification and quantification methodology through application of new developments in molecular biology; 8. Facilitate predoctoral and postdoctoral training. In summary, the ITF provides the EHSRC with a facility with expertise in inhalation toxicology and aerosol physics, particularly for organic dusts and bioaerosols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--PULMONARY BIOLOGY Principal Investigator & Institution: Hunninghake, Gary W.; Professor and Director; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 29-SEP-1990; Project End 31-MAR-2006 Summary: The Pulmonary Biology Core is headed by Gary Hunninghake, M.D.; Joel Kline, M.D., is the co-director. The focus of this core is on Environmental Lung Disease and the development of new science related to this area. The specific aims of the core are (1) to function as a training environment for young scientists interested in environmental lung disease (ELD) associated with agricultural exposures; (2) to support the research of young scientists to develop independent studies related to ELD associated with agricultural exposures; (3) to attract senior scientists to develop studies on ELD associated with agricultural exposures; (4) to consult with scientists pursuing studies related to ELD; (5) to enhance communication among investigators interested in ELD; and (6) to promote the use of dedicated EHSRC facilities for investigation of ELDs associated with agricultural exposures. The director and co-director of the core propose to meet on a monthly basis with the investigators of the Core. The purpose of these meetings will be to identify new investigators who can direct their careers to ELD. The leaders of this core also will organize bimonthly seminars to discuss ongoing research, and they will evaluate and support meritorious requests for pilot studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CTGF IN LUNG FIBROGENESIS Principal Investigator & Institution: Lasky, Joseph A.; Associate Professor of Medicine; Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 05-JUN-2001; Project End 31-MAY-2005 Summary: (Applicant's Abstract): The formation of scars within the lungs (pulmonary fibrosis) frequently leads to shortness of breath, disability and even death. The clinical

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outcome for the vast majority of patients with idiopathic pulmonary fibrosis (IPF) remains poor. It is likely that identification of specific disease mechanisms at the molecular level will provide the best avenue for development of novel therapies. One of the key cytokines in lung fibrosis is transforming growth factor beta 1 (TGF-beta1). TGFbeta1 expression is upregulated in several models of fibroproliferative lung disease. We propose that TGF-beta1's stimulatory effect on interstitial matrix accumulation is mediated through a novel cytokine, connective tissue growth factor (CTGF). CTGF is a newly described peptide that shares several profibrogenic activities with TGF-beta1, namely as a promoter of collagen and fibronectin synthesis, as a mitogen for mesenchymal cells, and as an inducer of cell adhesion. A recent investigation has shown that the CTGF gene promoter contains a TGF-beta1 response element. We have found that CTGF upregulates lung fibroblast alpha 1 type I collagen expression in vitro and that CTGF expression is upregulated during the development of fibrosis in the two animal models of lung fibrosis that we have studied. Our recent manuscript is the sentinel description of CTGF expression during lung fibrogenesis. The overall goal in this proposal is to directly test the hypothesis that: Connective tissue growth factor is a prominent regulator of collagen deposition in fibrotic lung disease. To test our hypothesis we will demonstrate the effect of recombinant CTGF on several key facets of type I collagen synthesis and degradation in vitro. We will determine, using CTGF transgenic mice and a CTGF adenoviral vector, whether overexpression of CTGF within the lung results in pulmonary fibrosis, both alone and in the presence of other fibrogenic cytokines. We will also employ the novel approach of using a hammerhead ribozyme in vitro and in vivo to study the effect of inhibiting CTGF synthesis on TGF-beta-mediated collagen synthesis and degradation. These studies will establish the role that CTGF plays in lung fibrogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOKINE GENE REGULATION IN BERYLLIUM DISEASE Principal Investigator & Institution: Newman, Lee S.; Professor; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: Inhaled environmental toxins can exert effects on the lungs by altering the function of key genes. In particular, hypersensitivity immune responses to metals, such as beryllium (Be), occur when moderate cytokine and growth factor expression. The consequences are granulomatous inflammation and fibrosis. The ability to find effective treatments of environmental lung diseases, such as chronic beryllium disease (CBD), will depend upon our understanding of molecular mechanisms underlying environmentally-induced regulation of immune cell gene function. T lymphocytes and macrophages accumulate in the lungs of CBD patients. Upon Be-stimulation in vitro, CBD lymphocytes proliferate and bronchoalveolar lavage (BAL) cells produce high levels (ng/ml) of TNF-alpha and IFN-gamma. We recently found that the -308 A TNF promote polymorphism is a functional polymorphism associated with high levels (>1.5 ng/ml) of Be-stimulated CBD/BAL cell TNF- alpha protein and that these high TNFalpha levels correlate with disease severity in CBD. TNF-alpha is a pro-inflammatory cytokine important to granuloma formation in the lungs but the precise molecular mechanisms cytokine important to granuloma formation in the lungs but the precise molecular mechanisms by which Be regulates the production of high TNF-alpha levels our unknown. Our data shown that IFN-gamma priming of macrophages leads to enhancement of Be-induced TNF-alpha. Using a mouse macrophage cell line (H36.12j) that mimics the CBD macrophage response we found that Be up-regulates TNF-alpha

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protein and mRNA. Be-stimulation did not up-regulate nuclear transcription factors. However, Be+ IFN-gamma co-stimulation significantly enhances TNF-alpha production and increased nuclear levels of NF-kappaB, AP-1 and CREB. Preliminary data suggest that isolated CBD/BAL macrophages can produce lower but significant amounts of Bestimulated TNF-alpha in the absence of BAL CD4+ T cells and without IFN-gamma. The central hypothesis of this study is that: 1) Be-antigen recognition (sensitization) alone does not result in CBD. 2) CBD results when Be triggers TNF-alpha over-expression. 3) TNF-alpha over- expression occurs because IFN-gamma and Be work in concert to upregulate TNF-alpha mRNA splicing and to increase nuclear transcription factors. 4) TNF-alpha over-expression will be highest in people who have the -308 A, TNF promoter polymorphism because IFN-gamma up- regulated transcription factors enhance TNF gene transcription in the presence of the polymorphism. Together with Beinduced mRNA splicing, high TNF-alpha levels will be produced. The objective of our study is to test these specific hypothesis using isolated CBD macrophages and macrophage cell lines. We will determine whether the key control subjects cells that do not make Be-stimulated TNF-alpha. We will determine if the -308 A promoter polymorphism in concern with the TNF gene 3' untranslated region (3'UTR), stabilizes Be-stimulated TNF-alpha mRNA transcripts, thus boosting TNF-alpha protein expression. With improved understanding of the cellular and molecular mechanisms that result in progression of macrophages from the BeS to CBD phenotype, we hope, in the future, to design preventative strategies to modulate disease in high-risk, exposed individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINANTS OF PANCREATIC INJURY IN CYSTIC FIBROSIS Principal Investigator & Institution: Accurso, Frank J.; Professor of Pediatrics; Children's Hospital (Denver) 1056 E 19Th Ave Denver, Co 80218 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): Marked phenotypic variability in individuals with cystic fibrosis (CF) who have the same CF genotype suggests that modifier genes may play a role in this disorder. Since most abnormalities in CF begin early in life, investigation of determinants of disease in infants and young children may provide insight into pathogenesis. We have observed that circulating immunoreactive trypsinogen (IRT) levels in infants with CF identified through newborn screening are correlated with early pancreatic dysfunction and with pulmonary function at six years of age. IRT is therefore a biochemical marker of early pancreatic disease in CF also carrying implications for early pulmonary disease. In addition, we have observed that IRT is heritable. We therefore hypothesize that early IRT abnormalities in CF are explained in part by genes that modify the CFTR gene effect on pancreatic injury. We will test this hypothesis in infants and young children with cystic fibrosis diagnosed through newborn screening. IRT will be modeled with age using longitudinal mixed effects approaches with a log transformation to produce a quantitative phenotype that will be used in a Transmission Disequilibrium Test (TDT) to determine if IRT is cosegregating with each of the candidate modifiers. Specific modifiers to be tested can be categorized as follows: a. Genetic markers lying within the D19S112 region on chromosome 19 that have been linked to intestinal disease in CF, b. Genes coding for pancreatic enzymes that are capable of causing local tissue injury, c. Genes coding for pancreatic proteins capable of modulating local tissue injury, d. Genes coding for pancreatic membrane transporters, and e.Putative modifier genes of other CF organ involvement. Candidate genes with common, known functional variants will be studied

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through genotyping. Genes with no known functional variants will be sequenced in a subset of patients exhibiting either "rapid" or "slow" decline in IRT to identify potentially useful mutations or polymorphisms. Sequences of interest will then be examined in the entire study population, with priority as follows: obvious mutations (for example nonsense, frameshift and splice type), then promoter or missense alleles, then variants non- randomly segregating among the IRT "rapid" or "slow" decliners, and then more common variants. We also plan to establish a clinical database and a DNA repository for infants identified by newborn screening. Achieving our goals will likely provide: 1. Insight into the mechanisms of early pancreatic injury, 2. Clues to the pathophysiology of other organs involved in CF, 3. Valuable prognostic information for counseling families of newly diagnosed infants, 4. Information useful for future investigation of the pancreatic complications of CF in later life including recurrent pancreatitis and cystic fibrosis related diabetes. Our long-term objectives are to find new approaches to the early treatment of CF in order to delay pancreatic injury and the development of lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EISOSANOID IMBALANCE IN FIBROTIC LUNG DISEASE Principal Investigator & Institution: Peters-Golden, Marc; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 26-DEC-2001; Project End 30-NOV-2006 Summary: (Applicant's Abstract) A growing body of evidence indicates that elcosanoid metabolites of arachidonic acid modulate the inflammatory, immune, and mesenchymal components contributing to pulmonary fibrosis. However, leukotrienes (LTs) promote all of these processes while prostaglandin E-, (PGE2) generally suppresses them. Of note, our laboratory has identified two separate abnormalities in eicosanoid synthesis in the lungs of patients with the fibrotic disease, idiopathic pulmonary fibrosis: namely, overproduction of LTs and underproduction of PGE2- Moreover, additional recent studies indicate that a similar eicosanoid imbalance characterizes animal models of pulmonary fibrosis, and that modulation of this imbalance by genetic or pharmacologic means attenuates fibrogenesis. The hypothesis of this proposal is that this pro-fibrotic imbalance of eicosanoid generation is centrally important in the pathogenesis and prognosis of pulmonary fibrosis. Furthermore, we hypothesize that this eicosanoid imbalance is exacerbated by treatment with corticosteroids, contributing to the disappointing clinical response of fibrotic lung diseases to these agents. The aims of the current proposal are to extend our understanding of the cellular and enzymatic mechanisms underlying this imbalance, its amenability to pharmacologic and/or genetic modulation, and the cytokines and (growth factors regulated by eicosanoids which influence the evolution of fibrotic lung disease. This will be accomplished by studying lung tissue and cells (macrophages and fibroblasts) from mice with bleomycin induced pulmonary fibrosis and from patients with pulmonary fibrosis. In the clinical studies proposed, eicosanoid abnormalities will be correlated with clinical severity, histologic classification, and course of disease. In addition, we will determine the effects of three treatment regimens for pulmonary fibrosis (prednisone, azathioprine plus prednisone, or the LT synthesis inhibitor zileuton) on eicosanoid synthesis, pathobiological mechanisms, and clinical outcomes. The proposed studies will critically evaluate a new pathophysiologic paradigm with important implications for therapy of this devastating group of fibrotic lung diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENZYMATIC DEFENSE, INFLAMMATION AND CHRONIC LUNG DISEASE Principal Investigator & Institution: Kourembanas, Stella; Associate Professor of Pediatrics; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (Applicant's Abstract) Chronic lung disease (CLD) of the preterm infant is characterized by a chronic fibroproliferative process associated with inflammation and disruption of normal alveolarization. Multiple cytokines and chemokines have been linked to the chronic inflammatory response leading to the development of CLD in humans as well as in animal models of this disease. Collaborative efforts from the group have shown that exposure of mice to extremes of oxygen tension (from 10% to 95% oxygen) resulted in lung injury characterized by a pronounced inflammatory response with mononuclear cell infiltration and dramatic induction of inflammatory cytokines/chemokines. Of interest, hypoxic mice overexpressing heme oxygenase-1 in the lung were completely protected from both inflammation as well as pulmonary vascular remodeling, a later consequence of hypoxia. Moreover, induction of inflammatory cytokines/chemokines was drastically suppressed in HO-1 transgenic mice. In this section of the SCOR application, the investigators propose 3 specific aims to extend these studies: In Aim 1, they will characterize the developmental response of the lung to injury leading to CLD. Using the newborn mouse model, they will characterize the inflammatory and architectural changes in response to hyperoxia, hypoxia, and infection that lead to CLD-like injury and analyze the effects of HO-1 induction in these developmental responses. In Aim 2, the investigators will investigate signaling pathways and molecular mechanisms by which HO-1 modulates cellular inflammatory responses. Using molecular biological techniques, they propose to analyze specific kinase pathways and transcriptional activities mediating cellular responses to injury. In Aim 3, the investigators characterize potential crosstalk between HO-1 signaling and CLD-relevant pathways in collaboration with SCOR investigators. Using transgenic mice or knockout models characterized by each member of the SCOR, they will investigate mechanisms of airway hyper-responsiveness in response to hypoxia, hyperoxia and infection; evaluate the role of chemokines in the animal models of CLDlike injury; and validate the animal findings to human disease by correlating HO activity with incidence, severity and complications of CLD in ventilated premature newborns. In achieving these aims, they will gain a better understanding of the immature lung?s defenses to injury and may be able to identify specific genes and pathways to target therapy for CLD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPITHELIAL GROWTH FACTORS IN ENVIRONMENTAL LUNG DISEASE Principal Investigator & Institution: Brody, Arnold R.; Professor; Pathology and Laboratory Medicine; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2002 Summary: This proposal focuses on the molecular mechanisms for inhaled inorganic particle-induced fibroproliferative lung disease (FLD). The central hypothesis being examined is that interstitial fibrogenic lung disease is mediated by the mesenchymal cell growth factors, PDGF, TGF-alpha, TGF-beta and TNF-alpha, that are synthesized and secreted by the bronchiolar-alveolar epithelium as a result of lung injury. Four

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specific aims are given to test this hypothesis. In aim 1, two strains of mice resistant to the fibrogenic effects of inhaled asbestos are used to determine if the temporal and anatomic expression of the genes and growth factors by the alveolar epithelium correlates with resistance. In aim 2 alveolar epithelial cells are isolated from these same mice strains to determine if the asbestos-resistance phenotype is maintained in vitro. In aim 3 the principal investigator proposes to focus on PCNA expression in cells capable of forming fibrogenic lesions versus those from resistant mouse strains. In aim 4 transgenic mice overexpressing human PDGF-B within the bronchiolar-alveolar epithelium and spontaneously developing fibroproliferative abnormalities in the lung will be crossed with asbestos-resistant strains to determine if the offspring have increased susceptibility to asbestos. This would implicate PDGF-B in fibrogenic lung disease and target this growth factor for antibody or gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FAMILY BASED ANALYSIS OF MODIFIERS OF CF LUNG DISEASE Principal Investigator & Institution: Levy, Hara; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Cystic fibrosis (CF) is an inherited multisystem disease characterized by progressive deterioration in lung function and pancreatic insufficiency attributed to dysfunction of a single gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). Although CF is considered a monogenic disorder, phenotype expression is considerably diverse even in patients with the same CFTR mutation. Patients with the most common mutation, delta 508 a deletion of a phenylalanine at position 508 of CFTR, often have markedly different clinical courses; some, have less aggressive lung disease and survive into their 50s, while others have a precipitous decline in lung function and die of respiratory failure in their early 20s. What accounts for this phenotypic heterogeneity is unclear. The goal of this proposal is to identify non-CFTR candidate genes that may impact the severity of CF lung disease and account for phenotypic heterogeneity. Any modifier gene identified will have important implications for defining the pathophysiology of CF lung disease, stratifying patients, and identifying new targets for therapy. To initially test our hypothesis, we propose to evaluate candidate genes that are immune-related and non-CFTR genes. Our strategy will use a family based association analysis to test for association of candidate genes to severity of pulmonary disease. We propose to combine new genotyping technology, well-powered samples, and a haplotype-based approach to comprehensively and definitively determine variation in the most promising candidate genes modifying CF lung disease. A unique contribution of this research will be the examination of genetic modifiers in CF in parent child-trios to evaluate polymorphisms in genes that may impact phenotype and hence CF lung disease. The overall hypothesis to be tested is that polymorphisms in genes associated with a well-defined phenotype represent modifying factors that account for the variability in expression of CF lung disease as measured by lung function, forced expiratory volume in one second (FEV1), in patients with the delta 508 genotype. To test this global hypothesis, we have established three specific aims: 1) Establish and characterize a CF database and define key features of the quantitative and qualitative components of our CF phenotype; relate phenotype to variation in disease severity as defined by levels of FEV1 adjusted for age and gender in CF patients homozygous for delta F508 CFTR allele. 2) Genotype single nucleotide polymorphic markers (SNPs) from five promising genes (selected based on data from Aim 1, the PGA, microarray analysis, and the literature) found to be

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associated with lung function in a sample of 100 individuals homozygous for delta 508 and identify common haplotypes and htSNPs that tag these haplotypes for these genes. 3) Genotype these htSNPs identified in AIM 2 in a sample of homozygous delta F508 individuals and their parents, and perform family based association analysis for CF phenotype and pulmonary function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE MODIFIERS IN CF LUNG DISEASE Principal Investigator & Institution: Knowles, Michael R.; Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Patients with cystic fibrosis (CF) display a wide range of disease severity, particularly in pulmonary phenotype. Although some of this variability can be attributed to specific mutations within the CFTR gene (allelic heterogeneity), much of this variability has not been adequately explained. The central hypothesis of this proposal is that much of the "severity" (or "mildness") of CF lung disease reflects the influence of non-CFTR "modifier" alleles (genes). This project is designed to identify associations between non-CFTR genes and the pulmonary phenotype. To accomplish this goal, we will study 600 CF patients who have the same CFTR genetic background, i.e., homozygous deltaF508, and who are at the extremes of pulmonary phenotype, i.e., the most severe and mildest lung disease. Pulmonary disease severity (or mildness) will be quantitated by longitudinal lung function analysis with informative censoring. The overall strategy will be to test for the association of candidate modifier alleles (genes) with the severity (or mildness) of - pulmonary disease. Key clinical features (gender; age-at-diagnosis; sweat Cl; nutrition; and respiratory microbiology) will be important variables in the overall analysis. Initially, we will test candidate genes (n=200) that have been implicated in the pathophysiology of CF lung disease. We will utilize a pooling strategy to expedite the first rounds of testing. After pooling DNA from the "severe" patients, and pooling DNA from the mild patients, we can identify those genes (alleles) with the greatest association with phenotype. Follow-up genotyping in individual subjects will allow subgroup analyses (gender; age-at-diagnosis; nutrition; respiratory microbiology) for each gene, as well as more complex analyses to search for interaction among different alleles. Subsequent studies will involve genome-wide testing with SNPs to identify loci (and genes) that are not present in the initial list of candidate genes. Identification of genes that modulate the severity of the pulmonary phenotype will improve our understanding of the pathophysiology of CF lung disease, and identify new targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC EPIDEMIOLOGY OF GLUTATHIONE AND CF LUNG DISEASE Principal Investigator & Institution: Mckone, Edward; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This proposal is a five-year training plan designed to prepare the Principal Investigator for a career as an independent patient-oriented researcher with an interest in the genetic epidemiology of lung disease. Through the

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completion of these projects as well as the pursuit of course work in clinical and genetic epidemiology, the candidate will develop the necessary skills to design and implement family-based genetic association studies, including gene-gene and gene-environment interaction. The proposal is a collaboration between the Division of Pulmonary and Critical Care Medicine and the Departments of Public Health Genetics and Environmental Health and includes experts in cystic fibrosis, genetic epidemiology, environmental health and toxicology. The primary scientific goal of this research is to analyze the genetic determinants of lung disease variability in patients with cystic fibrosis (CF). Aim 1 will be a retrospective cohort study, using the National CF database, to quantify the effect of CF genotype on CF clinical manifestations, including lung function and mortality. Aim 2 will be a prospective study to examine for linkage and association between severe CF lung disease and a candidate gene that influences glutathione synthesis. DNA will be collected from CF patients and their biological parents. Transmission disequilibrium testing (TDT) will be performed on the trios looking for unequal segregation of glutayl-cysteine-ligase catalytic subunit (GLCLC) polymorphisms from parents to CF patients with severe lung disease. Aim 3 will examine for an association between severe CF lung disease and polymorphisms of glutathione-S-transferase M1 and TNF-alpha also using a TDT. As these polymorphisms may influence glutathione synthesis and function, gene-gene interaction with GLCLC polymorphisms will be examined using a case-only study design and logistic regression. Finally, in aim 4, through the use of validated questionnaires and methods of residence location, environmental exposure to tobacco smoke and air pollutants will be measured to test for gene-environment interaction. These projects have strong clinical and public health implications both in terms of predicting high-susceptibility patients that may develop severe lung disease as well as increasing our understanding of the mechanisms of CF lung function decline. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC MODIFIERS OF CYSTIC FIBROSIS Principal Investigator & Institution: Boyle, Michael P.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 04-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Dr. Michael Patrick Boyle is an Assistant Professor in the Pulmonary and Critical Care Division of the Johns Hopkins School of Medicine. He is fully committed to an academic career investigating genotype and phenotype relationships in cystic fibrosis (CF). The mentor of this application, Dr. Garry Cutting, is a world-recognized expert in the genetics of CF, professor and director of graduate education at the McKusick-Nathans Institute of Genetic Medicine, and previous mentor of numerous successful K awards. The didactic and mentoring program outlined in this application is the result of close collaboration between Dr. Boyle and Dr. Cutting and will provide the foundation for Dr. Boyle's development as an independent investigator. CF is caused by mutations in the chloride channel CFTR. A wide range of severity of pulmonary disease is seen in CF individuals with identical CFTR genotypes, making it clear that CFTR genotype is not the main determinant of severity of CF lung disease. The overall goal of this proposal is to help identify the basis for variability of CF lung disease in individuals with identical CFTR genotype. We aim to answer: Do genes which modify the severity of CF lung disease exert their influence by altering the level of expression and function of CFTR, or through mechanisms unrelated to the underlying CFTR defect (e.g. inflammatory mediators, airway defense)? To do this we will determine if there is a difference in CFTR expression and function in the airway

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epithelium of homozygous delta F508 CF patients with mild and severe lung disease. First, we will use Nasal Potential Difference Measurement, the most sensitive in-vivo measurement of the ion-transport function of CFTR, to determine if there are differences in CFTR ion-transport. Second, because some cellular functions of CFTR are not reflected in these ion transport measurements, we will evaluate for differences in CFTR expression by comparing mRNA levels. These ion-transport and mRNA studies should allow us to determine if variability in CF lung disease is associated with alterations in level of expression and function of CFTR. Last, we will evaluate three of the strongest current CF candidate modifier genes to determine if the distribution of their functional alleles segregates with severity of lung disease in our CF clinic population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC RISK FACTORS FOR AIRFLOW OBSTRUCTION AFTER HSCT Principal Investigator & Institution: Clark, Joan G.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Bronchiolitis obliterans syndrome (BOS), a clinical syndrome of irreversible, progressive airway disease causing obstructive lung disease (OLD), is a serious complication of hematopoietic stem cell transplant (HSCT). Research investigating the pathogenesis of BOS suggests that this form of OLD is immune mediated and consistent with pulmonary graft versus host disease (GVHD). Since proinflammatory and anti-inflammatory cytokines play a significant role in the pathophysiology of GVHD and the production of these cytokines is influenced by environmental and genetic factors, we believe there are genetic determinants other than histocompatibility disparity that influence the risk of developing OLD after HSCT. This project will develop a new collaborative effort between investigators in lung medicine and immunology and genetic epidemiologists to utilize an existing source of stored DNA and a novel haplotypic approach in exploring the hypothesis that allelic haplotypes of genes in the lipopoly-saccharide (LPS) inflammatory pathway influence the risk of developing OLD after HSCT. Aim 1 will assess for the association of susceptibility as well as protective allelic haplotypes of genes in the LPS inflammatory pathway in both diseased as well as hypernormal individuals. The allelic haplotypes will be generated using the Phase program developed at the University of Washington. These haplotypes are generated by selecting for single nucleotide polymorphisms (SNPs) with an allele frequency ?10% that exist in significant linkage disequilibrium with each other. When multiple such haplotypes are considered for each gene, a nonbiased analysis of nearly the entire gene can be performed for association with a complex disease. Aim 2 will confirm the association and linkage of certain allelic haplotypes of the genes in the LPS inflammatory pathway with OLD using an established family-based study design, the transmission disequilibrium test. Father, mother, and proband offspring trios will be identified in our DNA resource for genotyping to determine if haplotypes found to be significantly associated with OLD in aim 1 are indeed genetically linked and associated with disease in a family based analysis. Use of allelic haplotypes will provide an unbiased look for association with disease throughout the entire gene and an opportunity to perform rigorous fine genetic mapping and gene discovery. Ultimately, this insight can be applied to understand inflammation and how it causes more common lung diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GM-CSF IS REQUIRED FOR MACROPHAGE SURFACTANT CATABOLISM Principal Investigator & Institution: Bonfield, Tracey L.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Idiopathic pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown etiology. PAP is characterized by the accumulation in the alveoli of surfactant material, which is thought to result from inefficient catabolism by alveolar macrophages and type II epithelial cells. The granulocyte macrophage-colony stimulating factor (GM-CSF) knockout mouse develops a PAP like syndrome, which can be resolved by pulmonary expression of GM-CSF. These observations led to the treatment of PAP patients with recombinant GM-CSF with a subset showing improvement of lung disease. Subsequently, it was determined that all untreated PAP patients had neutralizing antibodies against GM-CSF. In this context, PAP is an excellent disease model to illustrate surfactant catabolism and lung homeostasis as well as the dynamic relationship between the "bench" and the "bedside." Further, the integration of observations in the GM-CSF knockout mouse, to ex vivo studies at the bench, to dynamic in vivo PAP patient management decisions is an excellent foundation for the development of an independent "patient-oriented" scientist. In the GM-CSF knockout mouse, it has been shown that GM-CSF regulates monocyte/macrophage surfactant catabolism through the transcription factor PU.1. GM-CSF can induce activation and differentiation of monocyte/macrophages through peroxisome proliferator-receptor (PPAR() which has not been evaluated in alveolar macrophages. Our preliminary data shows that (1) anti-GM-CSF titer is diagnostic for PAP and it correlates with PAP disease activity in vivo (2) PAP alveolar macrophages ex vivo express less PU.1 and PPAR( than healthy control alveolar macrophages, (3) PAP alveolar macrophages ex vivo express less of differentiation markers CD14, TLR2, TLR4 and MR while the expression of certain pro-inflammatory cytokines GM-CSF, IL-6 and MIP-1a are elevated as compared to healthy controls. Based upon these data, we hypothesize that maturation and differentiation of human alveolar macrophages by GM-CSF through the activation of PPAR( and PU.1 is essential for surfactant catabolism. The specific aims are: (1) Evaluate the role of GM-CSF in regulating PPAR( and PU.1 in alveolar macrophage maturation, differentiation and surfactant catabolism; (2) To use the ongoing GM-CSFFDA clinical trial to evaluate changes in functional GM-CSF on monocyte/macrophage maturation, differentiation and surfactant catabolism. The translational focus of this proposal provides an ideal training environment for the development of "patientoriented" investigative skills. Laboratory observations will be interfaced with patient clinical course, thus contributing to dynamic patient management decisions. These studies are the first to address the role of GM-CSF in alveolar macrophage maturation, differentiation and surfactant catabolism and have the unique advantage of utilizing PAP patients involved in a FDA approved GM-CSF clinical trial as an in vivo model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GROWTH FACTORS AND SIGNALING PATHWAYS IN PF Principal Investigator & Institution: Worthen, G Scott.; Associate Professor and Senior Faculty m; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Pulmonary fibrosis is an idiopathic interstitial lung disease with high mortality. The illness is characterized by abnormal intraparenchymal

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deposition of collagen, with focal accumulations of fibroblasts, myofibroblasts and young connective tissue that are found in unique locations within the affected lung. We propose that aberrant responses of fibroblasts to growth factor and cytokine signaling underlie the progression of disease, and may represent appropriate targets for therapy and markers of response. Using a combination of broadbased techniques, the gene expression patterns of lungs and fibroblasts from patients with pulmonary fibrosis and controls will be discerned using novel algorithms allowing analysis of many thousands of genes per sample. Expression not only of relevant gene products but also signals reflecting response to growth factors and cytokines will be measured in tissue microarrays, where a single protein will be examined in hundreds of tissue samples. The activation state of distinct lung cellular compartments, defined in a fashion not previously feasible in tissue samples from human disease, will be mapped in patients and controls. The secretion of distinct proteins that reflect fibroblast origin and response to stimulation will be pursued both in vitro, but also using bronchoalveolar lavage as a window on secretion by lung cells. New proteomic techniques to enhance throughput and reduce variation will allow elucidation of BAL-derived proteins that reflect disease behavior. The result will be a set of targets plausibly involved in excessive fibroblastic response to signals, and in vitro evidence as to the potential success of intervention strategies. New biomarkers reflecting prognosis, nosology, and response to therapy will be discerned, potentially improving the yield of new trials. The data should advance our ability to treat and monitor pulmonary fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST-PATHOGEN INTERACTIONS IN CYSTIC FIBROSIS Principal Investigator & Institution: Moskowitz, Samuel M.; Pediatrics; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 05-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The goal of this application is to establish the independent research career of the candidate in the study of chronic lung disease, including that affecting individuals with cystic fibrosis (CF). The candidate is a pediatric pulmonary fellow with the career goal of developing an active program of diseaserelated basic research as a faculty member at a medical school. The training environments are the laboratory of the sponsor, Dr. Samuel Miller, at the University of Washington School of Medicine, and the CF Center at Children's Hospital and Regional Medical Center in Seattle, directed by the co-sponsor, Dr. Ronald Gibson. The proposed project seeks to clarify molecular mechanisms underlying chronic lung infection and inflammation in individuals with CF. The opportunistic pathogen Pseudomonas aeruginosa (PA) infects the lungs of most individuals with CF, frequently (but not invariably) causing severe progressive lung injury and premature death. Study of the interaction between PA and the CF lung is necessary to understand both the cellular processes that promote or permit CF lung infection, and the precise means by which PA interacts with lung cells to cause airway damage. The structure of lipopolysaccharide (LPS), the principal constituent of Gram-negative bacterial surfaces, appears to play a pivotal role in both microbial and human aspects of this interaction. The candidate's preliminary results indicate that resistance of laboratory and clinical isolates of PA to antimicrobial peptides (key components of host innate immunity) correlates with alterations in the structure of the lipid A moiety of LPS. Moreover, mutation of a PA locus that regulates LPS-modifying enzymes influences the antimicrobial peptide resistance phenotype. The microbiological phase of the project thus seeks to define PA genes necessary for this putative resistance mechanism, and to identify potential

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inhibitors using antimicrobial peptide-resistant strains. The human phase of the project builds on the clinical observation that some individuals with a severe CF genotype and chronic PA airway infection nevertheless have minimal lung disease. A case-control design will be utilized to test the hypothesis that polymorphisms in innate immune genes may limit CF lung disease. Those innate immune genes encoding the LPS receptor are leading candidates as CF modifier loci, based on the recent finding that CFspecific PA LPS structures have increased inflammatory activity. When prevalence of an LPS receptor variant differs in mild and severe CF lung disease, receptor function will be assayed in cell culture models of LPS signaling. Identifying innate immune genes as modifiers of the CF lung phenotype may suggest new avenues for treating the inflammatory consequences of CF airway infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMAGE AND MODEL BASED ANALYSIS OF LUNG DISEASE Principal Investigator & Institution: Hoffman, Eric A.; Professor; Radiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: With the emergence of innovative interventions in lung disease both at early and end stages of the disease (i.e.: retinoid therapy or lung volume reduction surgery for emphysema and receptor blocking therapies for lung cancer), it has become clear that sensitive, objective, accurate and repeatable measures must be developed to determine presence and regional distribution of lung abnormalities. Standard pulmonary function tests are inadequate for the task. While x-ray CT has been accepted as the most likely single modality providing a comprehensive regional lung assessment, visual scoring of the radiographs have proven to be inadequate, given the requirements of objectivity, repeatability and sensitivity. As helical scanners emerge with the ability of acquiring multi-slice data sets in less than a heart beat, the possibilities of assessing both structure and function simultaneously further limits the utility of a visual image assessment. We propose a Bioengineering Research Partnership, bring together a team of Engineers, Scientists, and Physicians from 6 academic institutions to collaborate in developing the technologies which will allow for the use of dynamic, volumetric x-ray CT to assess the lung. At the core of the research program will be a state-of-the-art helical CT facility that will evolve over the course of the proposal towards true dynamic volumetric imaging capabilities. We propose to develop a model of the normal human lung for three decades of adult age. This model will consist of an atlas of the normal anatomy down to the sub-lobar segments. Attached to these sub-lobar segments will be parameters of the normal range and distribution of airway, blood vessel, tissue, blood flow, and ventilation properties assessed at two standardized airway pressures. In addition, this model will provide normal ranges for image-based measures of chest wall mechanics and their coupling with regional lung compliance. Also attached to the model will be global parameters (PFT's, Broncho- Alveolar Lavage, exhaled Nitric Oxide). To assess the accuracy of such an approach, we focus on smoking related lung disease: specifically emphysema and cancers with assessment focused both in patients with known disease as well as in a comparison of nonsmokers and smokers with normal pulmonary function tests. The accuracy of the individual measures to be developed under this proposal will be verified in normal animals using both isolated and in-vivo lungs and using a dog model of emphysema. We hypothesize that such a comprehensive model, based upon measurements from non- invasive, dynamic, volumetric imaging can be built for the human lung and applied to the early, preclinical assessment of lung abnormality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNOGENETIC AND EXPOSURE FACTORS IN BERYLLIOSIS Principal Investigator & Institution: Maier, Lisa A.; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The interplay between exposure and genetic susceptibility has not been defined for many disease processes. This project will focus on exposure and genetic factors which result in beryllium disease, serving to better define risk factors in this disease process, while also providing a model of gene and environment interactions for other environmental lung disease. Inhalation of beryllium particular triggers sensitivity to beryllium (BeS) and the granulomatous lung disease chronic beryllium disease (CBD) in 2-10% of exposed workers. A polymorphism in the human leukocyte antigen (HLA) DPB1 containing a glutamic acid at amino acid position 69 (Glu69), has been found in 85-97% of CBD cases compared to 30-45% of beryllium exposed non-diseased (Be-nondiseased) controls. Preliminary data show that Glu69 is also associated with BeS, suggesting that Glu69 plays a role in the immune response to beryllium, not the development of disease per se. It is likely that BD is a multi-genetic disease, with a number of susceptibility factors determining BeS, CBD and more progressive forms of CBD. To date, information on other genetic susceptibility factors is limited, as is the relationship between genes and exposure. Preliminary data presented in this proposal indicate that high TNF-alpha levels, associated with an exaggerated immune response in CBD and more severe disease, are related to the TNF promote variant with an A at position -308 (-308A). The central hypothesis of this study is that immune susceptibility factors, including Glu69 and the -308A TNF promoter variant, interact with each other and with exposure factors in the development of BeS, CBD and more severe CBD. Preliminary data support the hypothesis that by increasing beryllium-stimulated TNFalpha to high levels at the anatomical site of disease, the 308A allele may tip the scale in the direction allele may tip the scale in the direction of granulomatous inflammation, eventually resulting in progression from BeS to CBD and more severe diseases. The proposed study will determine if there is an interaction between the polymorphism associated with the development of the beryllium specific immune, Glu69, and a polymorphism associated with an increased inflammatory response via TNF-alpha, the 308 variant. Furthermore, this project will define exposure variables important in the development of BeS and CBD, and the relationship between these exposure variables and the Glu69 and -308A susceptibility genes in BeS and CBD risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATION IN THE CF LUNG Principal Investigator & Institution: Davis, Pamela B.; Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-SEP-1998; Project End 31-AUG-2003 Summary: This SCOR has its ultimate goal the cure of cystic fibrosis (CF). The studies proposed are based on the premise that understanding the origin and control of the inflammatory response in the CF lung is critical for CF therapeutics at many stages of the disease. It is our hypothesis that inflammation occurs early in the course of the CF lung disease, and must be controlled in order for other treatments to achieve maximum effectiveness. Six projects revolved around this central theme. In project 1 (P. Davis, project leader) CF mice and cell lines expressing the CF phenotype are used to explore the relationship between the CF phenotype and the inflammatory response to the most common infecting organism in CF- Pseudomonas aeruginosa. Dr. Prince's project 2 will

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investigate the activation by calcium of NF-kappaB, which is a central molecule in the inflammatory response. This transcription factor is activated by pseudomonas and regulates many of the inflammatory responses observed in CF, and appears to be activated in the basal state in some patients with CF. How calcium regulates NF-kappaB and how it participates in the pathogenesis of the CF lung disease is the focus of her project. Dr. Drumm's project 3 investigates potential modifier genes for CF that he has identified in mice and will identify in man, and will study not only how they affect salt transport but also how they affect the ability of the animal to respond to an infectious stimulus. Dr. Berger's project 4 investigates the role of the anti-inflammatory cytokine IL-10 in the pathogenesis of the CF inflammatory lung disease, and evaluates IL-10 as a possible therapeutic intervention. In collaboration with Dr. Konstan, he will investigate the inflammatory response early in life in CF infants and young children, as well as using animal models to determine the nature and pathophysiologic importance of this cytokine. Dr. Ferkol's project 5 will capitalize on what we have learned about the epithelial cell as a modulator and regulator of the inflammatory response and will test novel therapeutic approaches to the protection of the surface of the epithelial cells. Dr. Tosi's project 6 will investigate the relationship between the infection and inflammation in the CF lung and the effectiveness and toxicity of adenoviral mediated gene therapy. These projects will be supported by an Administrative Core and an Animal Core, directed by Dr. Richard Woychik, and will draw on other cores and investigators from the Cystic Fibrosis Research Center at Case Western Reserve University. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFLAMMATION, MATRIX DISRUPTION AND CHRONIC LUNG DISEASE Principal Investigator & Institution: Ekekezie, Ike; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2001; Project Start 07-SEP-1999; Project End 31-AUG-2004 Summary: This application seeks five year funding for the K-23 Award: PatientOriented Research Career Development. The principal investigator, Ikechukwu I. Ekekezie, M.D., is currently Assistant Professor of Pediatrics, University of MissouriKansas City School of Medicine, Attending Neonatologist, Children's Mercy Hospital, Kansas City. The mentor for this proposal is William E. Truog, M.D., Professor of Pediatrics, University of Missouri Kansas City School of Medicine. The overall objective of this proposal is to provide the necessary support for the evolution of Dr. Ekekezie's career from that of a new productive investigator into an independent physician scientist investigating pathogenesis and treatment of chronic lung disease of prematurity. The application brings together three elements: 1) an able and active clinician-candidate for research career development (Dr. Ekekezie); 2) a superb physical and intellectual environment for clinical and applied research; and 3) the most common, but poorly understood, neonatal pulmonary disorder remaining: chronic lung disease of prematurity (CLD). The improvement in mortality afforded by prenatal corticosteroid and by post-natal surfactant therapy has increased the prevalence of CLD. No current therapy, such as anti-elastase or antioxidant therapy, appears to reduce significantly the severity of CLD. Comprehensive understanding of its pathobiology is lacking. Dr. Ekekezie is currently investigating the use of inhaled nitric oxide to ameliorate CLD. He has a supplement to R-01 HL58125, which has funded his studies examining inflammation and matrix injury in CLD. He has helped design a complex clinical trial as a proposed Co-Investigator for a trial currently under review (R-01 HL62514). He has developed expertise in the biology of extracellular matrix proteins including laminin,

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and in pro-inflammatory cytokines and their contribution to the evolution of CLD. The clinical study proposed for this application is to examine the disruption of the basement membrane and extracellular matrix by metalloproteinases (MMPs) in CLD and to examine the effects of nitric oxide and corticosteroid therapy on MMP activity in CLD. Therapy with anti-MMP agents may then be studied. Appropriate use of potential new therapies will necessitate evaluation of timing, dosage, side effects, and interactions with concomitant therapies. The often unhappy history of therapeutics in neonatology demands that the most critical thinkers available use their skills in the application of new treatments to sick newborn infants. The investment in Dr. Ekekezie represented by this Award - coupled with his own enthusiasm, skills, intelligence, and high oral standards -- ought to result in his being propelled into the next generation leadership group in this area. The K-23 Award mechanism is an ideal way to advance him from here to there. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHALED NO FOR THE PREVENTION OF CHRONIC LUNG DISEASE Principal Investigator & Institution: Kinsella, John P.; Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 29-SEP-2000; Project End 31-AUG-2004 Summary: Inhaled nitric oxide (iNO) therapy is a safe and effective treatment for term newborns with persistent pulmonary hypertension and hypoxemic respiratory failure. However, little is known about the potential role of iNO in the treatment of premature newborns with respiratory failure. Premature newborns are particularly susceptible to the adverse effects of ventilator- induced lung injury, oxygen toxicity, and lung inflammation which contribute to the development of chronic lung disease (CLD). Despite treatment with exogenous surfactant and steroids, CLD remains a major cause of morbidity and mortality in premature newborns. Early clinical observations suggest that low-dose iNO improves oxygenation and decreases the need for mechanical ventilator support in the premature infant. In addition to its effects on gas exchange, recent laboratory and clinical observations suggest that iNO may also act as a lungspecific anti- inflammatory treatment and reduce the contribution of lung inflammation to the evolution of acute and chronic lung injury in premature infants. We recently conducted a masked, randomized, controlled pilot study of low- dose iNO in premature newborns with severe hypoxemic respiratory failure. Eighty patients from 12 centers were randomized to treatment with iNO (5 ppm) or placebo. Low-dose iNO caused acute improvement in oxygenation and reduced ventilator days. Moreover, important trends in CLD reduction were noted in this pilot trial, without an increased incidence of adverse events (e.g. intracranial hemorrhage). Based on the beneficial effects of iNO on gas exchange and lung inflammation, we hypothesize that early treatment with lowdose iNO may reduce the incidence of CLD in premature newborns with respiratory failure. To test this hypothesis, we have designed a multicenter, randomized, controlled, masked trial without crossover. Specific aims of this study are to determine if: l) iNO reduces CLD in premature newborns (gestational age<34 weeks and birth weight 5001250 grams) with respiratory failure requiring mechanical ventilation in the first 48 hours of life; 2) early serum and tracheal aspirate markers of inflammation are reduced by iNO therapy and predict recovery without CLD; and 3) to assess the safety of iNO. We estimate the incidence of CLD to be 40% for this population. A 25% reduction in CLD disease occurred in our pilot trial. We estimate that a similar reduction in CLD could be achieved in less severely ill newborns. To permit an 80% chance of detecting a

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25% reduction in CLD with iNO treatment (40% reduced to 30% with equivalent mortality), 400 patients will be randomized in each group (total n = 800). With 10 centers participating and enrolling a minimum of 30 patients per center per year, the study enrollment duration would be 2 years, 8 months. This study design also allows for insights into the role of inflammatory markers in prediction of CLD risk in the premature newborn. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FIBROSIS

INTERFERON-GAMMA

IN

EXPERIMENTAL

PULMONARY

Principal Investigator & Institution: Enelow, Richard I.; Associate Professor and Chief; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Chronic fibrotic lung disease occurs in a variety of clinical settings, including the idiopathic interstitial pneumonias, as well as in many of the rheumatic diseases. We previously developed a model of acute T cell-mediated pulmonary injury, which results in severe alveolar injury, leading to significant respiratory impairment and death within a few days. This model involves the adoptive transfer of activated CD8+ T cells into recipient animals expressing the specific antigen on alveolar epithelial cells. In contrast with the acute lung injury occurring after transfer of wild-type CD8+ T cells, we have recently found that chronic inflammation and fibrosis may result from the CD8+ T cell recognition of alveolar antigen in the absence of IFN-gamma exclusively in the antigen-specific cell population, and have found that these T cells induce a totally different pattern of lung injury, including a more chronic pattern of inflammation and, importantly, interstitial and intraluminal fibrosis. This was accomplished by using IFN-gamma-deficient CD8+ T cell clones for adoptive transfer, which results in inflammation and fibrosis that evolves over a period of 2-4 weeks after administration. This very exciting result represents the first animal model of pulmonary fibrosis that does not involve an exogenous toxin, and which evolves entirely from a single, well-defined molecular interaction, the T cell receptor recognition of antigen on alveolar epithelial cells. In order to understand the mechanisms which underly the resolution of acute pulmonary inflammation which results directly from expression of IFN-gamma by the antigen-specific CD8+ T cell, and the factors which may lead to chronic inflammation and fibrosis in its absence, we propose the following Specific Aims:1. To characterize the impact of IFN-gamma expressed by CD8+ T cells on input and host T lymphocyte activities in vivo.2. To characterize the specific effects of IFNgamma expressed by CD8+ T cells on host macrophages and the impact on progression to chronic pulmonary inflammation.3. To characterize the specific effects of CD8+ T cell recognition in the absence of IFN-gamma on antigen-presenting epithelial cells and the impact on progression to chronic pulmonary inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LATENCY AND REACTIVATION TUBERCULOSIS Principal Investigator & Institution: Bishai, William R.; Associate Professor; International Health; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 30-APR-2007 Summary: (provided by applicant): Mycobacterium tuberculosis is remarkable in its ability to infect the human host and remain quiescent for many years only to reactivate

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when host defenses are suppressed. One-third of the global population is latently infected with tuberculosis, yet this clinically inactive state when bacilli are often noncultivatable is poorly understood and inadequately characterized. Appropriate animal models that more accurately mimic human diseases are needed to test vaccine candidates, and to understand the complex relationship between mycobacteria and host. The currently available animal models in mice and guinea pigs are characterized by multibacillary disease and are distinguished by the host response. Mice mount a poor delayed type hypersensitivity response and develop chronic lung disease, eventually succumbing to a progressive granulomatous pulmonary disease with high bacillary load. Guinea pigs also have a multibacillary disease, but are exquisitely susceptible with rapid hematogenous dissemination and a strong DTH response that results in rapid lung inflammation, destruction and death. Paucibacillary latent disease can only be induced with the administration of antibiotics. In contrast, rabbits are relatively resistant to aerosol infection with M. tuberculosis and mount a granulomatous response that effectively contains the bacilli. Over the course of 6-l2 months, all culturable bacilli disappear. In addition, the histopathologic response is remarkably similar to that of humans pointing to the rabbit model of tuberculosis as a promising avenue by which to study stage-specific changes in both host and bacilli. In this application, we will aerosol infect rabbits and allow the granulomatous lung lesions to regress to latency. With the use of immunosuppressive agents such as corticosteroids, iNOS inhibitors, and specific anti-cytokine antibody, we will reactivate infection. In parallel, we will refine the in vitro granuloma assay using rabbit white blood cells to have an in vitro model with which to correlate and compare our in vivo results. Harvesting serum and rabbit tissue at various stages of infection, we will characterize the stage-specific host humoral and cell-mediated immune responses. Understanding the antibody expression profile during latent disease may lead to important diagnostics in a disease hampered by diagnostics with low sensitivity and specificity. In addition, we will analyze the transcriptional bacterial response to various disease stages using microarrays and RT-PCR with molecular beacons. Finally, we will use a transposon mutant library to identify clones that are impaired in specific stages of infection. Appropriate animal models are critical to the successful development of tuberculosis vaccines, new drugs and better diagnostic tests for tuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF MORBIDITY/MORTALITY DUE TO AIR PARTICLES Principal Investigator & Institution: Godleski, John J.; Associate Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 28-JUN-1997; Project End 30-JUN-2003 Summary: Recent epidemiologic studies show that exposures to particulate air pollution, far below the current National Ambient Air Quality Standards, are associated with increased morbidity mortality in people with cardiopulmonary disease. This project focuses upon discovery of mechanisms by which inhaled ambient particles may produce such effects. Studies from our laboratories have shown: 1) inhalation of concentrated ambient particles (CAPs) results in as high as 37 percent mortality in animals with pre-existing pulmonary inflammation, but no mortality and no detectable effects on the lungs of normal anamils; 2) with exposure to environmental particles, suing our sensitive technology, significant cardiac electrophysiologic alterations are found even in normal animals; 3) CAPs initiate production of oxidants and cytokines in

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inflammation-primed lung cells comparable in magnitude to highly toxic alpha-quartz, and reactive oxygen species directly induce pro-inflammatory cytokines. Concepts basic to our approach are: 1) ambient air particles should be used for study; 2) the exposed populations should model affected human populations; and 3) the adverse effects should include increased mortality and morbidity observed in people. The central hypothesis is: Ambient air particles are complex mixtures with intrinsic toxicity. In concert with pre-existing inflammation, particulate exposure results in stimulation oflung receptors, release of reactive oxygen species, and pro-inflammatory mediators that lead to local and systemic effects, which ultimately account for the epidemiological associations. Our studies will utilize: 1) the Harvard Ambient Particulate Concentrator, a newly developed device that can increase ambient particle concentrations up to 30X without changing the physical or chemical characteristics of the particles; 2) an urban aerosol typical of the northestern US with ambient fine particle concentrations usually 515 gu/m3; 3) animal models of chronic bronchitist, coronary heart disease, and asthma to simulat affected human populations and to elucidate mechanistic effects; 4) established cell, molecular, and systems physiology methods to test mechanistic hypotheses; and 5) analytical capabilities to relate specific particulate constituents to adverse responses. The study consists of 3 projects and 3 cores: 1) Air Particles Cause Death in Animals with Lung Disease; 2) Cardiac Vulneraability due to Ambient Air Particle Exposure; 3) Responses of Inflammation-Primed Lung Cells to Particles; and Ambient Particle Exposure and Characterization Core. The novel application of these technique in coordinates studies will offer new insights into mechanisms of toxicity of ambient air particles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BASIS OF LYMPHANGIOMYOMATOSIS Principal Investigator & Institution: Henske, Elizabeth P.; Associate Professor; Fox Chase Cancer Center Philadelphia, Pa 19111 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Lymphangiomyomatosis (LAM) is a lung disease affecting women with a distinctive histologic pattern of diffuse smooth muscle proliferation and cystic degeneration of the lung interstitium. LAM can occur in the absence of systemic disease ("sporadic LAM") or in women with tuberous sclerosis ("TSC-associated LAM"). Tuberous sclerosis (TSC) is an autosomal dominant syndrome characterized by seizures, mental retardation, and tumors of the brain, kidney, heart, and skin. LAM affects about 5 percent of women with TSC. TSC is associated with mutations in two genes: TSC1, on chromosome 9q34, and TSC2, on chromosome 16p13. TSC1 and TSC2 appear to be tumor suppressor genes. TSC1 or TSC2 loss of heterozygosity has been demonstrated in several types of TSC tumors, including renal angiomyolipomas. One objective of this proposal is to investigate the genetic mechanisms leading to smooth muscle proliferation in LAM. We have found absence of tuberin immunoreactivity in some cases of both TSC-associated and sporadic LAM. This is consistent with the "two hit" tumor suppressor gene model. To understand whether LAM fits this model, we will analyze LAM cells for clonality and loss of heterozygosity. We will also determine whether a relationship exists between specific types of TSC1 or TSC2 mutations and the development of LAM. A genotype-phenotype correlation might explain the fact that only 5 percent of women with TSC get LAM. Another objective of this proposal is to determine the relationship between sporadic LAM and TSC. Renal angiomyolipomas, which are benign tumors consisting of fat, smooth muscle, and dysmorphic vessels, occur in 70 percent of patients with TSC and in 40 percent of women with sporadic

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LAM. We found chromosome 16p13 (TSC2) loss of heterozygosity in renal angiomyolipomas from 7 women with sporadic LAM. This suggests that some women with sporadic LAM have underlying TSC2 gene mutations. These mutations could be either germline or somatic. We anticipate that this project will elucidate the genetic mechanisms leading to LAM. The long-term goals of this work are to understand the roles of TSC1 and TSC2 in cellular pathways controlling normal smooth muscle growth and differentiation, and to determine how disruptions in these pathways lead to disease. This work may lead to new diagnostic and therapeutic strategies for women with LAM, and may also have relevance to other diseases involving smooth muscle growth, including pulmonary fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR SPHINGOMYELINASE

CHARACTERIZATION

OF

A

LUNG

Principal Investigator & Institution: Goldkorn, Tzipora; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-MAY-2005 Summary: Molecular and Cellular Characterization of Sphingomyelinase, a Regulator of Ceramide Path and Apoptosis in the Lung Reactive oxidants, such as hydrogen peroxide (H2)2) and peroxynitrite (ONOO-), are strongly associated with lung epithelium injury and with the increased incidence of lung disease. Yet, the cellular and molecular mechanisms that link exposure of lung cells to oxidants with the development of lung disease are poorly understood. Our previous work has shown that oxidants modulate the function of upstream receptors and therefore exert growth control on airway epithelial cells. Recently, we have shown that H2O2- mediated oxidative stress modulates ceramide, a second messenger in cellular processes, to induce apoptosis in the bronchial epithelium. These results support our hypothesis that there is coupling between oxidative stress, the ceramide/sphingomyelin pathway, and induction of apoptosis in airway epithelial cells. To test this hypothesis, we will first characterize the effects of oxidative stress on the ceramide pathway at the cellular level. We will elucidate the cellular sites of interaction and determine which sphingomyelinase (SMase) isozyme is regulated by reactive oxidants to induce apoptosis. Then, we will purify and cloe the specific SMase which acts as the coupler between oxidative stress and ceramide-mediated apoptosis. This will allow our studies to progress from cellular to molecular characterization of the mechanism(s) underlying the regulation of ceramide generation and apoptosis. Characterization of oxidant-mediated ceramide generation at the cellular level, followed by isolation of the pure SMase protein and gene are important milestones that would link this pathway to lung injury at the cellular and molecular levels. In the long run, this direction will lead to more precise targets for clinical intervention to control apoptosis in lung epithelial cells, thus preventing epithelial injury, a major problem in lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PATHOLOGY OF CHRONIC LUNG DISEASE Principal Investigator & Institution: Gerard, Craig J.; Professor and Director; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2003; Project Start 15-JUL-1994; Project End 30-JUN-2007 Summary: (provided by applicant): In this continuation proposal, we seek to expand our understanding of the role of the complement system in chronic lung disease. During the

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last funding period, we created strains of mice with targeted deletions of the receptors for C5a and C3a anaphylatoxins. Our initial characterizations demonstrated that C5a is intimately involved in lung host defense and acute lung injury, but may demonstrate anti-inflammatory properties as well. Unexpectedly, characterization of the C3a receptor -deficient mice demonstrated a significant role in a model of allergic airways inflammation and bronchial responsiveness. This observation has been subsequently reproduced in guinea pigs and correlative data from humans. By contrast, conflicting data have emerged in mouse and rat studies with C5 and C5a receptor in allergen induced airways hyperresponsiveness. We hypothesize that C3a and C5a are broadly involved in chronic lung diseases, including asthma and bacterial infection, extending beyond neutrophil and macrophage mediated injury to airway epithelium and smooth muscle. In addition, new preliminary data demonstrating up regulation of the cytokine early T cell activator/osteopontin synthesis in bone marrow in response to C5a suggests a mechanistic link between innate and adaptive immunity and may be related to the mechanism of C5a mediated host defense. Significant gaps in our knowledge of the system remain, however. In this renewal, we will address three specific aims. Aim 1 will investigate the mechanism by which C3a receptor deficiency is protective in models of airways responsiveness. Aim 2 will address the issue of C5a receptor in the control of allergic airways hyperresponsiveness. Aim 3 will investigate the C3a and C5a receptors in models of lung defense. Understanding the role of anaphylatoxins in models of lung disease and host defense will provide the proof of principle necessary to advance therapeutics in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTIDISCIPLINARY TRAINING PROGRAM IN LUNG DISEASE Principal Investigator & Institution: Toews, Galen B.; Chief and Associate Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-JUL-1993; Project End 30-JUN-2008 Summary: (provided by applicant): This application is a competitive renewal for a Multidisciplinary Training Program in Lung Disease. Its goal is to provide training in basic and clinical sciences relevant to the study of pulmonary disease. The program proposes to support 12 postdoctoral fellows (M.D.s and Ph.D.s) per year. The focus of the training program is a two year experience in the laboratory under the close supervision of a faculty trainer, utilizing molecular, cellular, animal modeling, epidemiologic, or clinical approaches. The program utilizes faculty trainers from the Departments of Internal Medicine (Divisions of Pulmonary/Critical Care Medicine and General Medicine), Pediatrics (Hematology/Oncology), Pathology, and Radiology. The program also utilizes faculty trainers form the Departments of Epidemiology and Biostatistics at the University of Michigan School of Public Health. Faculty trainers either have extensive research experience in diverse, but interrelated areas of cellular and molecular biology or in biostatistics, epidemiology, clinical research design or medical economics. All faculty trainers have trained postdoctoral fellows who have subsequently gone on to independent, productive careers in research and teaching. New facilities and faculty have been incorporated into this program to offer outstanding training opportunities in the disciplines of modern biology and the disciplines relevant to rigorous clinical research. The program provides a structured curriculum that contains appropriate course work, exposure to relevant lecture series, and an in depth intensive laboratory and/or clinical research experience. A broad range of research topics is available to trainees, including chemokine biology, the pathobiology of fibrotic

42

Lung Disease

lung disease, host defense mechanisms, lymphocyte-macrophage interactions, epithelial cell biology, fibroblast biology, protease biology, arachidonic acid biochemistry, granulocyte biology, pulmonary epidemiology, molecular genetic studies of candidate genes influencing susceptibility to lung disease, outcomes in lung disease, quality improvement, physician decision making, economic assessment of medical interventions, appropriate utilization of medical technology, financing and organization of medical care, medical ethics, and medical education. Continuation of this training grant in lung disease at the University of Michigan will capitalize on the exceptionally strong resources that have been assembled at this institution. The program, as constructed, will produce a cadre of well-trained investigators devoted to understanding the pathogenesis and treatment of pulmonary diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MURINE MODELS TO IDENTIFY CF LUNG DISEASE MODIFIERS Principal Investigator & Institution: Drumm, Mitchell L.; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Man and mouse are currently the only two species that display cystic tibrosis and both can demonstrate significant variation between affected individuals. It seems clear that at least some of the variation is genetic in nature, prompting the use of genetic strategies and state of the art molecular technology to find the genes involved. The restriction of CF to mouse and man limits the choice of model systems one can use to identify genes that modify cystic fibrosis. Of the two, human is obviously the more relevant model to study, but there are significant limitations to carrying out genetic studies in humans. Therefore, the mouse can be used as an adjunct to human studies, providing the ability to control both genetic and non-genetic factors not possible with humans. The drawback, however,.is that one may potentially sacrifice relevance, as there may be CF-associated characteristics between the two species that pertain little to each other. If a model system, such as the mouse, is used to identify genes relevant to CF, it would have the highest chance of success if the phenotypes studied are also relevant to CF, whether it be at the clinical, cellular or biochemical level. In this application we propose to exploit the benefits of the mouse systems by identifying loci that modify CF or CF-related phenotypes. In a related application, we will determine if the human homologues of those genes influence CF in humans. To achieve the goals of this application, the first specific aim is to map loci causing variation in mice for traits relevant to CF, such as those involved responses to Pseudomonas aeruginosa, and CFdependent growth retardation. Our preliminary findings on ion transport genetics indicate multiple genes are involved in the observed variation. For those traits showing multiple contributing loci, we wish to know the contribution of individual loci and how they interact with each other. Therefore, the second aim is to generate congenic mice for loci identified in Aim 1 and related projects by backcrossing and intercrossing consomic mice. Congenics will be generated on both on CF and nonCF backgrounds. Altering CFTR levels appears to have a significant phenotypic effect in patients, but regulatory mechanisms of CFTR expression are poorly understood. We have found tissue- and strain dependent differences in Cftr expression, allowing the potential identification of Cftr transcriptional regulators. Toward this end, the third aim is to identify transcriptional control elements of the Cftr promoter and corresponding transcription factors. The overall goal is to identify genes that affect, or can be manipulated to affect, disease severity in CF patients. To reach that goal, the genes in question must be isolated and their human counterparts identified for study. For this,

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43

the final aim is:to identify genes controlling phenotypes in Aim I and controlling expression in Aim 3, as well as their human homologues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROPEPTIDES AND CHRONIC LUNG DISEASE IN NEWBORNS Principal Investigator & Institution: Sunday, Mary E.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (Applicant's Abstract) The overall hypothesis is that bombesin-like peptide (BLP) is an early mediator of lung injury in bronchopulmonary dysplasia (BPD). Human infants with BPD have increased numbers of pulmonary neuroendocrine cells (PNECs) containing BLP. Elevated BLP could mediate lung injury in BPD, including interstitial fibrosis and reactive airways disease. The new data indicate that premature infants with elevated urine BLP levels at days 2-5 of age have a 10-fold increased risk of BPD, even when normalized for all other variables including prematurity. Elevated urine BLP levels also occur shortly after birth in 2 baboon models of BPD, in which BLP levels correlate with severity of subsequent chronic lung disease (CLD). Postnatal therapy with anti-BLP monoclonal antibody 2A11 protects against BPD in both models. The investigators propose to address the overall hypothesis using three Specific Aims. In Aims #1 and #2, they will test the hypotheses that hyperoxic newborn mice provide a valid model of CLD with similarity to specific features of human BPD. The investigators will determine how BLP contributes to lung injury in the murine model, and whether intratracheal BLP triggers specific pro-inflammatory cascades that also characterize hyperoxic CLD. The investigators will characterize histopathological changes over time, analyzing PNECs, mast cells, eosinophils, fibrosis, and alveolarization, and the kinetics of urine BLP and serum tryptase levels. They will assess BLP blocking antibody (2A11) as a prophylactic agent for CLD in the mouse model and evaluate which BLP receptors might be involved in mediating hyperoxic CLD using mice deficient in GRP-R, BRS-3, and/or NMB-R. In Aim #3, they will explore the role of BLP as a mediator of CLD in collaboration with other SCOR investigators. The investigators will analyze clinical factors associated with elevated urine BLP in premature infants, and estimate relative numbers of mast cells and eosinophils as compared to BLP levels in human infants with CLD. Finally, they will compare the course of hyperoxic CLD in genetically altered newborn mice with over-expression and/or deficiency of heme oxygenase-1, CRH, syndecans, or a panel of pro-inflammatory molecules including CCR3, CXCR3, NK-1R, and CDl0/NEP 24.11. These studies will help to clarify cellular and molecular mechanisms by which BLP could contribute to the pathophysiology of BPD, and facilitate the development of novel prophylactic treatments for infants at risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUSCEPTIBILITY

NICOTINE

ABUSE

/SMOKING-RELATED

DISEASE

Principal Investigator & Institution: Hoidal, John R.; Chief, Pulmonary Division; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): OBJECTIVE: The goals are to determine how nicotine contributes to the dysregulated inflammation and abnormal repair that leads to chronic obstructive lung disease (COPD), the link of nicotine addiction to COPD and the genetic basis for the development of COPD. HYPOTHESIS: We hypothesize that

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Lung Disease

many of the effects of smoking on the lung including the dysregulated inflammatory response and impaired repair that lead to COPD are mediated, in part, by functional alterations induced following the interaction of nicotine with nicotinic acetylcholine receptors (nAChRs) expressed on leukocytes or resident lung cells. We also hypothesize that polymorphisms in nAChRs couple with other common gene-based polymorphisms to increase susceptibility to COPD. SPECIFIC AIMS: The first aim will characterize nAChR expression on leukocytes and selected resident lung cells, and will determine the relationship between receptor expression and cell function. It will test the hypothesis that nicotine's ability to induce inflammation and inhibit repair are dependent on the pattern of nAChR expression on leukocytes and resident lung cells. The second aim will correlate patterns of nAChR expression in inbred mouse strains to susceptibility to COPD. It will test the hypothesis that susceptibility to emphysema in mice is determined by the pattern of nAChR expression. The third aim will determine the relationship between nicotine receptor expression and lung function decline in cigarette smokers. It will test the hypothesis that the pattern of leukocyte nAChR expression predicts lung function decline in COPD subjects. The fourth aim will identify genetic factors that play a role in the development of COPD, focusing, in particular, on the relationships between the genetics of nicotine addiction and those of COPD. It will test the hypothesis that polymorphisms in nAChR couple with other common gene-based polymorphisms to increase susceptibility to COPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL PA1-INHIBITORS OF NEUTROPHIL PROTEINASES Principal Investigator & Institution: Day, Duane E.; Molecular Innovations, Inc. 21315 Hilltop St Southfield, Mi 48304 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Neutrophil elastase and cathepsin G are serine proteases stored within the primary granules of neutrophils. The activation and degranulation of neutrophils at inflammatory sites result in the release of these proteases where they encounter inhibitors that regulate their activity in certain inflammatory conditions. These proteases have been implicated in the pathogenesis of a variety of diseases. One example of an inflammatory disease associated with neutrophil recruitment is Chronic Obstructive Pulmonary Disease (COPD). COPD is a slowly progressive and incurable disease of the airways, characterized by a gradual loss of lung function. An estimated 20.9 million Americans are currently affected by COPD; of which 18.3 million suffer from chronic bronchitis and 2.7 million suffer from emphysema. Our Phase I study involved the development of two rationally designed mutants of Plasminogen Activator Inhibitor One (PAI-1). The normal targets for PAl-1 are the plasminogen activators tPA and uPA. The gene for PAl-1 has been altered to produce mutants with altered protease specificity. These two new mutant inhibitors now target neutrophil elastase and cathepsin G. Due to the unique properties of PAl-1, these mutants actually exhibit properties superior to the natural inhibitors Alpha One Proteinase Inhibitor and Antichymotrypsin. Specifically, these mutants both inactivate and facilitate the cellular endocytosis and degradation of the neutrophil proteinases in the presence of polyanionic surfaces such as heparin and DNA, which sequester these very basic enzymes. The DNA that codes for these mutants has been cloned into a E. coli bacterial construct for expression at very high levels, and a patent pending method for the purification of PAl-1 will be scaled up in our Phase II study. The Phase II proposal extends and expands our studies to include: improving the properties of the mutants for therapeutic use, further characterization of the performance of the mutants compared

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45

with commercially available and endogenous inhibitors in a number of animal models, development of sensitive and specific immunoassays for neutrophil elastase and cathepsin G and, a study to examine the large scale production of the PAl-1 mutants using a rapid patent pending purification process. Destructive lung diseases are a major cause of morbidity in the U.S. We believe that these mutants can be developed into therapeutic agents for the treatment of a variety of inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF CF AND PCD LUNG DISEASE Principal Investigator & Institution: Noone, Peadar G.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 10-JUL-2000; Project End 30-JUN-2005 Summary: The goal of this clinical research project is to increase the understanding of the molecular, cellular, and organ-level pathogenesis of non-asthmatic airways disease, which will lead to better diagnosis and treatment of lung disease. The mucociliary apparatus is a major component of normal airway host defense, which depends on the integration of airway epithelial regulation of ion composition and volume of airway surface liquid, and ciliary structure and fiinction. Cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) are two genetic models of lung disease, which lead to abnormal airway clearance and chronic lung disease. The research project is sub-divided into two major components. Specific Aim I will define the relationship between mutant CFTR and expression of lung disease at a molecular, cellular and clinical level. In specific aim II, work will focus on defining the genetic mutations associated with PCD, including rigorous quantitation and definition of different cell biologic and ciliary ultrastructural phenotypes in PCD, to allow testing initially via the candidate gene approach. These research goals will be undertaken in the overall context of career development for clinical research in human subjects, with emphasis in the initial years of funding on course work and completion of the projects related to CF. Later years of funding will concentrate on the research in PCD. Thus, the research will combine practical experience in human research with coursework in genetics, molecular biology techniques, biostatistics, clinical study design, and the responsible conduct of human research. The work will be supervised by a senior clinical investigator mentor. Training will also be provided by collaboration with experts in a variety of fields, including molecular biology, clinical genetics, electrophysiology, and cell biology. The environment at UNCChapel Hill is rich in resources for this clinical research career development, offering formal courses, and experts in a variety of patient-oriented research fields. This award will greatly enhance the future ability of the applicant to conduct independent, highquality clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOGENESIS OF CHRONIC PULMONARY HYPERTENSION Principal Investigator & Institution: Meyrick, Barbara O.; Professor of Pathology and Medicine; Pathology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-JUN-1993; Project End 31-JUL-2003 Summary: The development of chronic pulmonary hypertension (CPH) is often secondary to other chronic lung diseases, such as congestive heart failure, obstructive lung disease, lung fibrosis and the acute respiratory distress syndrome. To develop more effective treatment for these patients, its pathogenesis must be more fully

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Lung Disease

understood. In this application, we propose biochemical, physiological, cellular and molecular studies to examine the role of the endothelin-1/endothelin converting enzyme (ET-1/ECE) system of pulmonary artery smooth muscle cells to the pathogenesis of CPH. We will use a chronically catheterized model of CPH, the sheep receiving continuous air embolization (CAE) into the pulmonary artery for these studies and smooth muscle cells isolated from the intimal (L1) and inner medial (L2) layers of the main and mid-region pulmonary artery from control and hypertensive animals. The following hypotheses will be tested: a) local levels of ET-1 contribute to the onset of CAE-induced CPH; b) cell-and site-specific differences in the ET-1/ECE system and ET1 receptors of normal main and mid-region pulmonary artery modulate smooth muscle cell function; c) cell and site-specific alterations in the ET-1/ECE system and ET-1 receptors contribute to the structural and functional changes of CPH; d) the L1 cells are more synthetically active than the L2 cells and L2 cells are more responsive to exogenous ET-1; e) ECE gene expression and activity in L1 and L2 cells is modulated by ET-1; and f) local synthesis of growth factors modulates the ET-1-stimulated ET-1/ECE system. We propose two specific aims to address these hypotheses. The first will determine whether alterations in cell- and site-specific differences in the ET-1/ECE system and ET-1 receptor populations in normal main and mid-region pulmonary artery contribute to the onset of CAE-induced CPH. The second will determine whether the ET-1/ECE system and ET-1 receptors are distinct in L1 and L2 cells isolated from main and mid-region pulmonary artery from control and hypertensive sheep, and whether exogenous ET-1 modulates the ET-1/ECE system and, in turn, whether growth factors, e.g., transforming growth factor-beta and insulin-like growth factor-1 modulate ET-1 stimulated ET-1 synthesis. Such studies will contribute to our understanding of the pathogenesis of CPH and ultimately to the development of new and novel therapies for this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PNEUMONIA

PROGNOSTICATION

IN

IDIOPATHIC

INTERSTITIAL

Principal Investigator & Institution: Flaherty, Kevin R.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 19-DEC-2001; Project End 30-NOV-2006 Summary: (provided by applicant): It has been proposed that idiopathic interstitial pneumonia (IIP) be divided into histopathologic categories. The overall prognosis differs between histopathologic categories; however, individual patients within categories can have an unpredictable response to therapy and survival. The potential for disease progression despite therapy often leads to the early listing of patients for lung transplantation as the mean time on the waiting list is 2-3 years. There is a shortage of donor lungs and this approach can lead to overpopulation of the waiting list and has the potential of preventing allocation of organs to the patients with the greatest need. This project will examine prognostic factors in patients with IIP and use these factors to develop a model that predicts survival. This model will help patients and physicians decide on optimal timing for lung transplantation. The histologic type of IIP is the most important, although not exclusive, factor influencing survival. Determination of histologic type requires a surgical biopsy which is not possible in all patients. Semiquantitative high resolution CT (HRCT) scoring for the amount of fibrosis also gives prognostic information. A drawback of this technique is observer variability, which could limit widespread utilization. We will collaborate with the University of Iowa to utilize a computerized quantitative scoring system which quantifies HRCT patterns

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(ground glass, fibrosis) present in the lungs of patients with IIP. We hypothesize that a computerized technique to determine the baseline and serial change in the amount of fibrosis will provide key prognostic information for patients with IIP. It has been suggested that radiologists can accurately diagnose categories of IIP. We will utilize survival analyses to compare the impact of a histologic diagnosis compared to a HRCT diagnosis for patients with IIP. We hypothesize that radiologists will have moderate accuracy in the diagnosis of IIP and that a HRCT diagnosis will provide more prognostic information when compared to a surgically obtained histopathologic diagnosis. The change in a clinical, radiographic, and physiologic (CRP) scoring system after three months of treatment also influences prognosis. A drawback is the requirement of a cardiopulmonary exercise test. We hypothesize that a scoring system utilizing the change in oxygen saturation during a six-minute hall walk will provide equal information without the need for a cardiopulmonary exercise test. During the past 10 years patients undergoing CRP testing have also performed a six-minute walk test. This information will be utilized to develop a new exercise component for a modified CRP scoring system. We will utilize survival analysis to define the patient population most likely to have improved survival through lung transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROPHYLAXIS OF ADRENAL INSUFFICIENCY TO PREVENT CLD Principal Investigator & Institution: Watterberg, Kristi L.; Pediatrics; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2001; Project Start 20-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): Chronic lung disease (CLD) is a frequent complication of prematurity, resulting in increased health care costs, prolonged hospital stay, frequent rehospitalizations, and compromised growth and development. Early treatment with dexamethasone may decrease CLD; however, this therapy has serious immediate and long-term adverse effects. Lung inflammation is a prominent early finding in the development of CLD. At the same time, many small premature infants show biochemical evidence and clinical signs consistent with adrenal insufficiency in the first week of life. Based on the hypothesis that early adrenal insufficiency results in amplified responses to inflammatory stimuli, and other physiologic disruptions, leading to ongoing lung injury and CLD, a randomized, blinded, placebo-controlled pilot study of 40 extremely low birth weight infants (ELBW, 500-999 g birth weight) was conducted. This study showed that hydrocortisone prophylaxis against adrenal insufficiency during the first two weeks of life resulted in a significant increase in survival without chronic lung disease. No increases in adverse outcomes were noted; however, the pilot study was not powerful enough to rule out a Type II error. Based on that hypothesis and pilot study, this application proposes a multicenter, randomized trial of 712 ELBW births, to further define the benefits and assess the risks of hydrocortisone prophylaxis against adrenal insufficiency in these infants. Primary outcome measures will be (1) benefit: increased survival without CLD at 36 weeks postmenstrual age; (2) risk: no increase in cerebral palsy at 18 22 months adjusted age. Other measures of neurodevelopmental outcome will also be assessed. The sample size will detect a change of 10 percentage points in successful outcome, and in the incidence of specific adverse effects, with a power of 80%. The hydrocortisone dose will be 1mg/kg/day for 12 days (equivalent to <10% of the typical starting dexamethasone dose), then 0.5mg/kg/day for 3 days. Baseline data on mother and infant, daily clinical data for the first 28 days of life, outcome data at 36 weeks postmenstrual age, and outcome data at 18 - 22 months adjusted age will be collected. Cortisol and cytokines (IL-1B, 1L6, and ILS) will be

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Lung Disease

assayed at baseline and at 6 days of life. After therapy, cortisol response to ACTH will be assayed. If this study confirms the benefits seen in the pilot study, it will result in a significant improvement in health care for premature infants, both by introducing a beneficial new therapy, and by avoiding higher dose dexamethasone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PULMONARY HYPERTENSION IN SCD Principal Investigator & Institution: Johnson, Cage S.; Professor of Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: Chronic lung disease and pulmonary hypertension are complications of the sickle diseases that are increasingly recognized and are associated with considerable morbidity and mortality. Standard therapy with oxygen and a hypertransfusion regimen have not demonstrated efficacy in prolonging survival in such patients, indicating a need for new approaches to management. Both hydroxyurea and L-arginine have the potential for increasing endogenous production of NO within the pulmonary vasculature and may have beneficial effects on oxygenation and pulmonary vascular resistance in patients with chronic lung disease and pulmonary hypertension. In addition, hydroxyurea improves red blood cell hemorheological properties and microvascular blood flow and thus combined therapy may impact smooth muscle hyperplasia in damaged pulmonary microvasculature. We hypothesize that beneficial clinical responses may accrue to patients with sickle chronic lung disease and pulmonary hypertension as a result of increases in NO generated by oral administration of hydroxyurea and/or L-arginine. We further hypothesize that these beneficial effects are consequent to modulation of vasoactive peptides (ET-1) and adhesion molecules (ICAM-I, V-CAM-I). The proposed research project is a phase II, randomized clinical trial designed to determine the effect of the NO donor L-arginine and hydroxyurea, either singly or in combination, on the biologic and clinical features of sickle cell disease patients with chronic lung disease and pulmonary hypertension. We further propose to characterize the effects of this treatment strategy on a broad range of RBC and hemorheologic properties in SCD,and to determine its efficacy in ameliorating chronic lung disease and pulmonary hypertension in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: QUALITY OF LIFE IN PATIENTS WITH SEVERE CYSTIC FIBROSIS Principal Investigator & Institution: Goss, Christopher H.; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by the applicant):Cystic Fibrosis (CF) is one of the most common inherited fatal diseases. Over the past thirty years, the median age of survival has improved from 14 years in 1969 to 29.1 years (95% Cl's 27.5 to 31.6) in 1999 in the United States. With this improved survival, this disease has been transformed from a disease with very high infant mortality to a disease that must now be considered a chronic and progressive lung disease. Improving the survival in these patients has been the primary goal over the last 30 years, but now clinical researchers must broaden their assessment of outcome in this disease to include patient-oriented outcomes such as health-related quality of life. Unfortunately, there is very limited research on the utility and relative strengths of different methods to measure health-related quality of life in patients with CF, especially for that group with the most severe disease. A better understanding of the

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best instruments, the minimal clinically important difference of these instruments, and the course of quality of life in these patients is needed in order to assess the value of treatments and interventions and to counsel patients and their families about their prognosis and the morbidity associated with this disease. This application proposes a prospective cohort study of patients with severe CF. Four different health-related quality of life instruments will be assessed, including a recently developed CF specific quality of life instrument. Patients will be evaluated at 6 month intervals f or a total of three years. The overall object of this proposal is to advance the state of the art in the measurement of health-related quality of life in adolescent and adult patients with severe cystic fibrosis in order to facilitate development and assessment of treatments that improve the quality of patients' lives and help predict the best time for evaluation for a lung transplant. In addition, this application proposes to compare the baseline differences health-related quality of life in patients not listed for lung or heart lung transplant, listed for lung or heart lung transplant, and transplanted and how healthrelated quality of life changes through time in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RARE LUNG DISEASE CLINICAL RESEARCH NETWORK Principal Investigator & Institution: Trapnell, Bruce C.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): We seek to a establish a research network that will facilitate clinical research in rare lung diseases by 1) promoting collaboration among centers already focused to clinical research on rare lung diseases, 2) attracting & training highly qualified investigators, 3) collecting clinical data from geographically distributed patients into a large, centralized database, and 4) making the accumulated clinical data available to those affected or possibly affected by a rare lung disease, their clinicians, clinical and basic investigators and the general public. Disorders chosen for the initial focus of this network include: alpha-1 antitrypsin deficiency (AATD), lymphangioleiomyomatosis (LAM), pulmonary alveolar proteinosis (PAP) and hereditary idiopathic pulmonary fibrosis (hIPF). The network consists of clinical centers in Ohio (the coordinating center), Colorado, Florida, Maryland, Massachusetts, Oregon, South Carolina and Texas, as well as in Japan and Australia. Centers are required to have and maintain an exemplary record of active clinical research and an adequate rare lung disease patient base. Participating patient support groups include the Alpha-1 Foundation, LAM Foundation and the Pulmonary Fibrosis Foundation. Many of these centers already work together closely. These centers and Foundations are also already closely integrated. For example, the Scientific Directors of all three participating foundations are active clinical investigators at clinical sites within the network. Furthermore, clinical sites were chosen from three currently active networks of collaborating clinical centers that include over 50 sites in 24 states distributed throughout the United States. All participating domestic clinical sites are associated with an active, NIH-supported general clinical research center (GCRC). Each center provides components required of the proposed network including ongoing longitudinal clinical studies, an excellent clinical training program, an active clinical research trials program designed to test novel therapies, develop diagnostic tests or evaluate outcome measures for rare lung diseases. Each of the Foundations provide education for patients, the lay public and the medical community. Importantly, one consequence of preparing this application has been the formation of the "Rare Lung Disease Foundation Consortium," which permits patient support groups with greater infrastructure to "nurture" the

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growth of less well-developed groups. It also provides support for individuals affected by a rare lung disease for which there is currently no foundation. Ongoing clinical, basic and translational studies at the centers chosen have already yielded critical insights into molecular mechanisms underlying lung function and defense in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ENAC BY SERINE PROTEASES IN AIRWAYS Principal Investigator & Institution: Donaldson, Scott H.; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 16-MAY-2002; Project End 30-APR-2007 Summary: This research career award is designed to develop the scientific skills of the primary investigator (PI), within the context of studying the regulation of the epithelial sodium channel (ENaC) by serine proteases in airways. Prior to the award, the PI has studied airway epithelial processes that mediate mucociliary clearance, have been at the forefront of cystic fibrosis (CF) and epithelial cell biology for a number of years. Recently, the PI and collaborators have begun to describe the impact that endogenous serine proteases activity located on cell surfaces has on ENaC function. With this award, the PI will identify specific components of this regulatory system (protease, antiprotease) and will elucidate the mechanism by which serine proteases regulate ENAC. Importantly, based on prior observations that specific properties of airway surface liquid effect ENaC function, the PI will test whether this exo-protease mediates ENaC responses to airway surface liquid tonicity and volume. Because of the tight link between ENaC function, airway surface liquid volume, and mucociliary clearance, these studies are expected to provide important information regarding how human airways respond to their local environment in a way that facilitates the maintenance of lung defense. Also, because ENaC hyperactivity underlies CF lung disease, insights gained in this area may be translated into new therapeutic approaches for this lethal genetic disease. The career development plan that will be followed includes training in specialized research techniques, such as immunohistochemistry, in situ hybridization, a broad range of biochemical techniques, and single ion channel kinetic analysis. Also, focused coursework and participation in an array of scientific meetings and seminars will be included. The PI's long term goals are to provide important new insights into the basic elements of airway defense, CF lung disease, and to bring these findings to the development of novel therapies for CF lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESEARCH TRAINING IN LUNG DISEASE Principal Investigator & Institution: Dickey, Burton F.; Professor and Chairman; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-JUL-1993; Project End 31-AUG-2008 Summary: (provided by applicant): The training program to be supported by this award will provide post-doctoral research training for fellows holding M.D. or Ph.D. degrees. The major emphasis will be basic research related to lung disease. Areas of expertise include molecular genetics, molecular and cellular biology, physiology and bioengineering. The major goal is to prepare scientists to work at the interface of physiology and cellular and molecular biology. The program is based in the Pulmonary and Critical Care Section of the Department of Medicine with a multi-disciplinary faculty including scientists with primary appointments in other administrative units. All of the faculty with primary appointments in the Pulmonary and Critical Care Section

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have joint appointments in one or more basic science departments. Most of the faculty are linked by collaborative research interests which have been strengthened during the previous periods of this training program. The faculty from other departments are senior scientists who, because of their scientific expertise have a strong interest in lung disease. Administrative units at Baylor College of Medicine include the Institute for Molecular Genetics, the Center for Leukocyte Biology, the DeBakey Heart Center, the Biology of Inflammation Center, the Center for Experimental Therapeutics, the Departments of Cell Biology, Molecular Physiology and Biophysics, Molecular Genetics and Pediatrics, and the sections of Cardiovascular Sciences; Allergy, Immunology and Rheumatology; Thrombosis; and Hypertension in the Department of Medicine. The Bioengineering laboratories at Rice University, the Director of which, is an adjunct Professor of Medicine at Baylor College of Medicine also participates. The program goal is to have approximately 60% of the trainees with Ph.D. degrees and 40% with M.D.s who have had at least one year of research training prior to being supported by the grant. The trainees are encouraged to apply for individual research fellowships for second and subsequent years, during the first year of grant support. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPIRATORY MECHANICS IN LUNG DISEASE AND SURGERY Principal Investigator & Institution: Loring, Stephen H.; Scientific Director of Respiratory Thera; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 30-JUN-2006 Summary: (provided by applicant): Chronic obstructive pulmonary disease (COPD) is a life-threatening, debilitating disease affecting more than 2 million Americans. New surgical therapies such as lung transplantation and lung volume reduction surgery (LVRS) can improve quality of life and pulmonary function in COPD. However, questions remain as to which patients are most likely to benefit from these therapies and why surgery is effective in some patients and not in others. We will continue an observational study of respiratory mechanics in a large cohort of patients with COPD before and after lung transplantation and LVRS. Our rationale is that our coordinated program of respiratory mechanical investigation will continue to provide insights and suggest useful measures of respiratory function that will reveal mechanisms of disease. Specific aims are: 1) To measure the maximal inspiratory pressure-volume characteristic of the chest wall in patients before and after lung transplantation or LVRS to assess changes in inspiratory function of the chest wall. We will test the hypothesis that inspiratory function of the chest wall is often compromised after operation, and that chest wall restriction is an important cause of failure to improve after LVRS or single lung transplantation for emphysema. If true, this finding would lead to studies of the origins and remedies of chest wall restriction after surgery. 2) To explore the differences between lung volumes measured by multiple breath helium dilution, plethysmography, and computed tomography (CT). Accurate measurements of lung volume are essential for diagnosis, for documentation of hyperinflation, for evaluation of patients before surgery, and for assessment of the effects of LVRS and transplantation. We will test the hypothesis that, contrary to current belief, helium dilution is more accurate than plethysmography in patients with COPD. If true, this finding would change clinical practice in this important group. 3) To develop methods to measure the pressure-area characteristics of the trachea in patients undergoing bronchoscopy and to determine whether the site of expiratory flow limitation in these patients is in the lungs or trachea. Acquired tracheomalacia is reportedly common in patients with COPD, and can cause severe expiratory obstruction that may be relieved by stenting or surgical reinforcement

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of the airway. We will test the hypothesis that many patients with demonstrated tracheomalacia and central airway collapse have obstruction caused by collapse of intrapulmonary airways, which is not amenable to surgical correction. Our findings will provide normative data on tracheal collapsibility not currently available, explore the association between tracheomalacia and COPD, and test a method for predicting the effect of stenting on expiratory obstruction in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ASL AND AIRWAY GLANDS IN CF LUNG DISEASE Principal Investigator & Institution: Verkman, Alan S.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Recurrent infection and deterioration of lung function are the major causes of morbidity and mortality in cystic fibrosis (CF). Although the genetic defect in CF was discovered in 1989, the mechanisms by which CFTR mutations cause lung disease in CF remain uncertain. This proposal focuses on the role of the airway surface liquid (ASL) and airway submucosal glands in CF lung disease. Our laboratory recently developed a series of novel fluorescent indicators and microscopy methods to measure ASL depth and composition, and submucosal gland secretion rate, fluid composition and viscosity. Aim 1 will determine whether ASL composition is abnormal in CF, focusing on lower airway function, clinically relevant stresses, and utilizing human tissues. Aim 2 will determine whether submucosal gland function is defective in CF, focusing on tissues that have not been subject to chronic infection and inflammation. Aim 3 will examine the hyper-absorption hypothesis (thinned, hyperviscous ASL in CF) and the defective oxygenation hypothesis (hypoxic ASL in CF). Some of the measurements will be done using intact human airways (normal vs. CF), including bronchoscopic biopsies obtained from pediatric CF patients before significant airway disease has developed. Some experiments will utilize potent small-molecule CFFR inhibitors and activators recently developed by our lab. The novel approaches and model systems should provide definitive data on putative abnormalities in ASL composition and submucosal gland function in CF. Understanding of lung disease mechanisms is of central importance in CF research, having direct implications for development of evaluation of new therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF NON-TUBERCULOUS MYCOBACTERIA IN LUNG DISEASE Principal Investigator & Institution: Stout, Jason E.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): Non-tuberculous mycobacteria (NTM) are emerging pathogens that cause a spectrum of clinical -manifestations, ranging from asymptomatic colonization to severe, progressive lung destruction. The organisms are ubiquitous in the environment, and it is often difficult to determine the significance of any particular respiratory isolate. Therefore, clinicians are as likely to ignore an isolate that is truly causing NTM pulmonary disease, as they are to prescribe inappropriate and often toxic therapy to patients who do not truly have NTM pulmonary disease but are only transiently colonized. The goal of our proposal is to increase our understanding of NTM pulmonary disease from both the microbe and host perspective. Our proposal is driven

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by two hypotheses. First, we hypothesize that specific, genetically related isolates of Mycobactefium intracellulare will be found to be associated with the disease state. Our first Specific Aim is therefore a case-control study of patients whose respiratory secretions grow the most common subset of NTM, the M. avium complex (MAC). We will examine mycobacterial isolates from patients with pulmonary disease due to MAC (cases) as well as isolates from control patients. The control patients have been selected from a group of individuals with only a single respiratory culture growing MAC and who are highly unlikely to have NTM pulmonary disease. In the laboratory, we will separate them into phylogenetically related groups using variations in the sequence of the 16S-23S internal transcribed spacer. The association between specific genetically related subgroups and MAC pulmonary disease will then be explored. Our second hypothesis is that, at a minimum, radiographicatly identified bronchiectasis will be associated with NTM pulmonary disease. Furthermore, we believe we can identify a combination of host (demographic characteristics, comorbidities) and microbial (species and genetic subgroup) factors that will strengthen the ability to predict which patients who grow an NTM from a respiratory site will have NTM pulmonary disease. We address this hypothesis in Specific Aim #2 by combining retrospective and prospective data from patients who grow NTM from respiratory specimens submitted for mycobacterial culture. After assessing patients' baseline demographics, comorbidities, and mycobacterial isolate (as described for the first hypothesis), we will prospectively follow the patients, collecting additional respiratory samples and clinical data. The primary outcome will be a diagnosis of NTM pulmonary disease, as defined by the ATS. This research combines classic and molecular epidemiological methods to form a basis for future investigations of host immune susceptibility to NTM, mycobacterial pathogenesis, and improved treatment options. Our findings will also assist clinicians in predicting which patients with NTM isolated from the respiratory tract will have NTM pulmonary disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF OXIDATVE STRESS IN CHRONIC BERYLLIUM DISEASE Principal Investigator & Institution: Day, Brian J.; Associate Professor; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The overall goal of this application is to understand the role of oxidative stress in chronic beryllium disease (CBD). CBD is an inflammatory hypersensitivity lung disease that continues to occur in 10% of the estimated 800,000 beryllium-exposed workers in the United Sates and is characterized by the presence of non-caseating granulomas with accumulation of macrophages and beryllium specific CD4+ T lymphocytes. Upon beryllium stimulation in vitro, these T cells proliferate and produce Th1 cytokines (i.e. TNF-?, INF-?, and IL-2) at unusually high levels. The precise molecular mechanism(s) by which beryllium regulates the production of these high levels of cytokines is unknown. It is hypothesized that oxidative stress enhances the APC's ability to present beryllium antigen to T cells, which may, in part, explain both the excessive cytokine response and associated lung granuloma formation. Exciting preliminary studies indicate that the redox status of the antigen presenting cell (APC) affects the T cell's response and may help explain why only a portion of the people exposed to beryllium actually develop CBD. The presence of APCs expressing class II molecules is required for CD4+ T cells from CBD patients to proliferate in the presence of beryllium in vitro. This project will use a modification of the clinical beryllium lymphocyte proliferation test (BeLPT) to examine the effect of redox balance on

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beryllium antigen presentation. This system will enable the testing of the hypothesis that oxidative stress affects the APC's ability to present beryllium antigen to T cells and the role of oxidative stress in modulating T cell activation. The hypothesis is addressed by the AIMS: (1) examine the effect of beryllium on APC and T cell antioxidant status and stimulation response; (2) examine the effect of altered APC glutathione status on beryllium antigen presentation; (3) examine the effect of altered oxidant status on beryllium antigen presentation by APC and T cell activation. Primary endpoints measured are (1) glutathione and enzymes involved in its synthesis and utilization; (2) markers of lipid, protein and DNA oxidation; and (3) T cell proliferation and Th1 cytokine release and accessory molecule expression. It is proposed that beryllium, itself; initiates oxidative stress in the APC and also serve as the antigen. Inherent differences in either resting APC antioxidant status or APC oxidant response to beryllium are predicted to be critical factors in determining whether people exposed to beryllium go on to develop CBD. These studies have the potential to further define the etiology of CBD, risk factors, and suggest novel approaches to prevent and treat this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF T CELLS IN LUNG DISEASE IN SYSTEMIC SCLEROSIS Principal Investigator & Institution: White, Barbara; Professor of Medicine; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-JUN-1995; Project End 30-JUN-2007 Summary: (provided by applicant): Pulmonary fibrosis is a major cause of death in scleroderma. Progressive pulmonary fibrosis in scleroderma is part of a mature, stable pathologic network that is ongoing in the lungs of certain patients, rather than the end of a unidirectional cascade. This pathology includes multiple components, linked in multiple ways. Preliminary work suggests that CD8+ T cells may be an essential component in this pathologic network. The hypothesis of this work is that T cells are essential to progressive pulmonary fibrosis in scleroderma, causing lung fibrosis through production of pro-fibrotic cytokines and growth factors as well as stimulation of TGF-betaa production and activation, alternative activation of macrophages and lung inflammation. The strategy is to delete T cells and monitor changes in profibrotic pathways in vivo, as well as clinical benefit on lung function. These experiments will include in-depth analyses of the effects of T cells on profibrotic pathways, assessed at the level of gene expression, protein expression and signal transduction. The expected outcome is that depletion of T cells will reduce T cell production of IL-4 and other profibrotic growth factors and reduce production and activation of TGF-beta. It will reduce alternative activation of alveolar macrophages and lung inflammation. These changes will be accompanied by arrest of pulmonary fibrosis. In this application, patients will receive alefacept therapy for 12 months, with bronchoalveolar lavage done at time 0, 6, and 12 months. Alefacept is a humanized LFA-3/IgG1 fusion protein that depletes CD2+ cells, which are largely T cells, through apoptosis, without T cell activation. The specific aims are given: 1) Show that alefacept therapy depletes T cells in the lungs of scleroderma patients and that T cell depletion stabilizes lung fibrosis; 2) Show that two major profibrotic pathways - IL-4 production and signaling and TGF-beta production, activation and signaling - are T cell-dependent processes in scleroderma lung disease; and 3) Show that alternative activation of macrophages and lung inflammation are T cell-dependent processes in scleroderma lung disease. The new information that is gained will advance knowledge of T-cell dependent mechanisms of pulmonary fibrosis in scleroderma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SIGNALING ALLERGIC LUNG DISEASE:NF-KB & T HELPER SUBSETS Principal Investigator & Institution: Aronica, Mark A.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2001 Summary: This proposal is part of a career development plan integrating didactics in the form of course work in immunology with direct, mentored experience in the design and conduct of scientific research. Expertise in these areas will provide the necessary components for a successful career in asthma research. The Center for Lung Research and the Department of Microbiology and Immunology at Vanderbilt University have the necessary facilities to complete the proposed research project. The mentors and faculty in this environment are well recognized, established senior investigators. The long term goal of this research is to investigate the mechanisms regulating the development and maintenance of atopic asthma and allergic diseases. T cell function is a critical determinant of immune responses as well as susceptibility to allergic diseases. Activated T cells can differentiate into effectors whose cytokine profile is limited to type 1 (IFN-gamma dominant) or type 2 (IL-4, IL-5 dominant) patterns. Type 1 T cell effectors serve to activate cell mediated immunity and inflammatory responses, while type 2 T cell effectors are involved in the humoral response and may limit or inhibit type 1 responses. The nature of an effector response can regulate emergence of disease states such as type 1 diabetes or asthma. These patterns of differential cytokine expression are controlled through transcriptional mechanism in T cell clones and primary effector cells. Experiments in specific aim 1 will investigate the mechanism by which NF-kappaB impairs type 1 T cell effector function. As part of this aim, I will investigate the role of impaired clonal expansion and quantitate cytokine defects. Experiments proposed in specific aim 2 will investigate if type 1 T cell effectors are required for the development of antigen- inducible airway hyperresponsiveness. In specific aim 3 we will use a dual TCR model to determine if an effector T cell repertoire can be biased through a second TCR so as to alter the susceptibility to antigen- induced airway hyperresponsiveness. This program together with the support of my mentor and co-mentor will provide me with the opportunity to become a successful independent investigator and will allow me to make a significant contribution to improving our understanding of allergic disease processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SITES OF ACTION OF INHALATIONAL ANESTHETICS ON HPV Principal Investigator & Institution: Baumgardner, James E.; Assistant Professor; Anesthesia; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-AUG-2003 Summary: This laboratory has been engaged in a systematic examination of the causes of perioperative hypoxemia. The work has demonstrated, quantitatively, the importance of hypoxic pulmonary vasoconstriction (HPV) for arterial oxygenation in health and disease, by the regulation of ventilation/perfusion ratios, as well as it's critical role in causing or contributing to pulmonary hypertension in acute and chronic lung disease. The induction of general anesthesia is associated with the development of dependent atelectasis. Normally HPV reduces the blood flow to atelectatic lung regions. However, inhalational, but not injectable, anesthetics variably inhibit HPV and oxygenation may become seriously compromised, particularly in the presence of lung disease or invasive techniques such as one-lung anesthesia for thoracic surgery,. Recent work by us and

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others have permitted the synthesis of an hypothesis that explains the fundamental HPV response in terms of pulmonary vascular smooth muscle cell properties. Following oxygen sensing the hypoxic response is a triphasic sequence with a transient Phase 1 constriction, a more or less transient (depending on wall tension conditions) Phase 2 dilation and a persistent Phase 3 constriction. Each of the Phases in the triphasic response can be understood in terms of the intracellular free calcium concentration (Ca2+), but the sources of the calcium combines features of both the electromechanical coupling of KCl induced constriction and the pharmacomechanical coupling of receptor agonist constriction but are not identical to either. Hypoxia Phase 1 is due to graded depolarization with Ca2+ induced Ca2+ release from the sarcoplasmic reticulum. Phase 2 is due to reuptake by the SR Ca2+ pumps and Phase 3 is due to increased force sensitization and some entry of Ca2+ through L-type sarcolemmal channels. The proposed studies will investigate the quantitative effects of inhalational and injectable (Propofol) general anesthetics on each step of this triphasic response. The methods employed will combine measurement of wall tension during exposure to hypoxia in isolated rat pulmonary arteries both intact and permeabilized and will measure intracellular Ca2+ using dye fluorescence as well as pharmacologic methods. Understanding the sites of anesthetic action is of fundamental importance but may also lead to improved patient management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SP-C MUTATIONS AND NEONATAL LUNG DISEASE Principal Investigator & Institution: Weaver, Timothy E.; Professor of Pediatrics; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract) Surfactant protein C (SP-C) is an extraordinarily hydrophobic peptide of 35 amino acids (Mr=3.5k) which facilitates rapid adsorption and spreading of surfactant phospholipids at an air-liquid interface. SP-C is synthesized in alveolar Type II epithelial cells as a 197 amino acid proprotein which is processed to the mature peptide by proteolytic cleavage of an NH2-terminal propeptide (residues 1-23) and a COOH-terminal peptide (residues 59-197). In human infants mutations leading to deletion of exon 4 in the COOH-terminal peptide or mutation of a single proline residue in the mature peptide are associated with development of interstitial lung disease (ILD). Although lung structure and function is not altered in SP-C (-/-) mice, the results of preliminary studies indicate that lung development is profoundly disrupted in transgenic mice expressing an SP-C transgene in which the NH2- and COOH-terminal peptides were deleted. This proposal will test the central hypothesis that alterations in SP-C proprotein or mature peptide structure lead to lung disease by disruption of lung structure via toxic effects related to aggregation and retention of SP-C in the early secretory pathway, or directly inhibiting surfactant function in the airspace. The specific aims of this proposal will determine if (1) specific mutations in the SP-C gene cause ILD in transgenic mice, (2) abnormal SP-C protein interacts with wildtype SP-C protein to promote lung disease, (3) specific mutations lead to aggregation and retention of SP-C in the early secretory pathway, and (4) secretion of abnormal SP-C protein contributes to lung dysfunction by inhibiting alveolar pulmonary surfactant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL INFLAMMATION

BASIS

OF

CD28 REGULATION

OF

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Principal Investigator & Institution: Green, Jonathan M.; Assistant Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: (Adapted from the Applicant's Abstract): T lymphocytes are a major component of the inflammatory response and aberrant regulation of T cell activation and differentiation may be central to the pathogenesis of asthma. The CD28 costimulatory receptor is a critical regulator of T cell activation and differentiation, and thus may be an important target for therapy of immune mediated diseases. Manipulation of this receptor has been shown to alter the course of several animal models of disease, inducing models of antigen-induced airway inflammation. Accordingly, the primary goal of this proposal is to increase our understanding of the cellular and molecular basis by which CD28 modulates the T cell response to antigen. CD28 regulates multiple aspects of T cell functions, including proliferation, adhesion, T helper cell phenotype development and cell survival. The PI demonstrates that CD28 is essential for the development of antigen-induced inflammation in a murine model of airway disease. Sensitized CD28-deficient mice fail to develop airway inflammation or eosinophilia in response to antigen challenge. Examination of T helper cell phenotype in CD28 -/- mice demonstrates a defect in Th2 cytokine gene expression. The mechanism by which CD28 regulates these diverse aspects of T cell function is poorly understood, but likely involves multiple signaling pathways. Studies in transformed cell lines have implicated specific domains in the cytoplasmic trail of CD28 as important in signaling, but no consensus exists as to what is required for CD28 function in primary cells or in vivo responses. The data in primary T cells demonstrates a requirement for specific proline mediated interactions with the non-receptor tyrosine kinase lck in the regulation of T cell proliferation by CD28. The PI hypothesizes that multiple distinct structural domains of CD28 modulate specific features of T cell activation and differentiation. To address this, the following specific aims have been proposed: 1) determine the structural features of CD28 required for co-stimulation of primary T cells in vitro; and 2) characterize the specific cellular and molecular determinants by which CD28 regulates airway inflammation in vivo. These studies will provide critical data as to the regulation of T cell directed immune responses, and provide a rational basis for the development of new therapeutic strategies in the treatment of inflammatory lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPPLEMENTAL SE AND VITAMIN E AND PULMONARY FUNCTION Principal Investigator & Institution: Cassano, Patricia A.; Div/Nutritional Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This proposed project is a randomized clinical trial testing whether supplementation with selenium and/or vitamin E affects pulmonary function. There is compelling evidence from observational epidemiologic studies that high antioxidant intakes are associated with reduced risks of chronic obstructive disease (COPD) and increased lung function. This proposal is an ancillary study to the multisite selenium and Vitamin E Cancer Prevention Trial (SELECT), a 4-arm placebo-controlled, double-blinded randomized trial in 32,400 men testing whether daily supplementation with vitamin E (400mg alpha-tocopherol), selenium (200 micrograms selenomethionine)

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or both vitamin E and selenium can prevent prostate cancer. We will enroll 3,000 SELECT participants for this respiratory ancillary study, and extend data collection to include pulmonary function, respiratory disease, and respiratory symptoms. We also will collect biological measures of nutrient exposure (serum vitamin E and selenium) and plasma lipids (total and high-density lipoprotein cholesterol) on all participants and oxidant burden (urinary F2-isoprostane) on a sub sample of heavy smokers and men with COPD. The primary outcome will be change between baseline and year 3 in forced expiratory volume in the first second (FEV1). FEV1 is a valid and reliable measure of respiratory function that strongly predicts COPD and mortality. Extensive data on diet and dietary supplement use are being collected by the SELECT parent study. All specific aims examine pre-specified contrasts between the 4 arms of the SELECT randomized trial. The underlying hypothesis is that antioxidants will reduce the age related decline in FEV1, and thus at the 3-year follow-up FEV1 will be higher in the groups receiving antioxidant supplements compared to controls. A secondary aim considers whether the effect of supplementation is greater among smokers (high burden of exogenous oxidants) who, by purposive selection of the study sites, will comprise 25% of the sample. The proposed study addresses important and timely questions about diet and lung disease, and makes cost efficient use of the research infrastructure of SELECT. This study could have enormous public health significance, because supplementation with antioxidant nutrients would be an inexpensive and practicable means to reduce morbidity and mortality from pulmonary disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURFACTANT PROTEIN C MUTATIONS:INTERSTITIAL LUNG DISEASE Principal Investigator & Institution: Beers, Michael F.; Associate Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Surfactant protein C (SP-C) is a 35 amino acid lungspecific hydrophobic peptide that enhances the biophysical activity of surfactant phospholipid. Recently, the importance of SP-C to lung health and disease has been underscored by the observations that heterozygous expression of over 14 different mutations in the SP-C gene in humans is associated with chronic interstitial lung disease (ILD), accumulation of unprocessed SP-C precursors, and selective absence of alveolar SP-C. The overall goal of this project is to further understand the molecular mechanisms underlying the consequences of mutant SP-C expression in the pathophysiology of interstitial lung disease. We hypothesize that mutations in the SP-C gene induce the development of interstitial lung disease by a pathway in which the aberrant protein products adopt nonnative conformations that lead to aggregation, mistargeting, generation of dominant negative effects and production of a toxic gain of function. The experimental approach involves both reductionist and integrative approaches to dissect out the consequences of key mutations in the SP-C sequence for the targeting and post-translational processing of proSP-C in the secretory pathway and to relate this back to the pathogenesis of ILD. The phenotype of mutant forms of SP-C described to date will first be functionally assessed in vitro with studies characterizing intracellular trafficking and processing using well characterized transfected cell line models (Aim 1). These results will then be extended to in vivo mouse models using transgenic expression of selected SP-C constructs to assess long-term effects of mutant proSP-C expression (Aim 2). In concert with Aims 1 and 2, the prevalence and functional significance of SP-C mutants in adult interstitial lung disease will then be assessed in a

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well-defined population of patients with interstitial lung disease using sequence based screening of genomic DNA (Aim 3). Abnormal SP-C sequences identified by this screening process will then be expressed in both the in vitro (cell-line) as well as the in vivo (transgenic mouse) model systems to develop a complete pathophysiological profile. This will permit a full functional assessment of a genetic etiology for ILD in humans through population-based screening coordinated with operational characterization of identified SP-C mutants expressed in the presence and absence of endogenous SP-C and in the context of both single cells and the whole animal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURFACTANT PROTEINS AND TYPE II CELL DIFFERENTIATION Principal Investigator & Institution: Ballard, Philip L.; Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 31-JUL-2006 Summary: (Applicant's Abstract) A deficiency of pulmonary surfactant at birth is a major contributing cause of lung injury and long-term lung disease such as bronchopulmonary dysplasia (BPD). The severe respiratory distress associated with inherited deficiency of surfactant protein-B (SP-B), in both mice pups and infants born at term, indicates a key role for the hydrophobic SPs in differentiation of type II cells. In the absence of SP-B there is a failure of normal lamellar body genesis as well as incomplete processing of SP-C. Recently, isolated deficiency of SP-C has been described in infants with interstitial lung disease. Respiratory distress also occurs in newborn term BWB calves which lack mature SP-C and have reduced SP-B, and in rodents respiratory distress and acquired deficiency of SP-B/-C occurs with lung injury secondary to bleomycin or infection (P. carinii and endotoxin). Based on these and other findings, this project proposes that synthesis of SP-B, SP-C and lamellar bodies are closely linked and that relative levels of both SP-B and SP-C influence surfactant function. The objectives of this proposal are to characterize the biosynthetic pathway for human SP-C, determine the roles of SP-B and SP-C in lamellar body genesis, and investigate SP-B and SP-C in lung disease. Aim I will determine expression of mature SP-C during type II cell differentiation in vivo and in vitro in relationship to production of SP-B and lamellar bodies and also define targeting domains and cleavage events in SP-C processing. The studies will utilize antibody to mature SP-C and a recently developed culture system for hormonally induced type II cell differentiation in vitro. Aim II will investigate the role and interactions of SP-B and SP-C in lamellar body genesis and trafficking of surfactant components using cell culture models of SP deficiency. The studies will examine the hypothesis that expression of mature SP-B is required for both lamellar body formation and final processing of SP-C intermediates. Experiments will be carried out in the cultured type II cell model and SP-B or -C gene expression will be selectively inhibited using adenovirus expressing antisense mRNAs. Processing and intracellular trafficking of each SP will be studied using epitope specific antibodies, pulse/chase labeling, and tagged recombinant proteins. In addition, processing and effects of alternatively spliced SP-B and mutated SP-C will be determined. Aim III will investigate expression of SP-B and SP-C in surfactant from infants with lung disease and after treatment with inhaled nitric oxide. It is hypothesized that a deficiency of SP-B and/or SP-C occurs in infants with severe BPD, and that this process is modulated by anti-inflammatory effects of nitric oxide. In addition, the developmental pattern for alternative SP-B splicing in human lung and relationship of splicing variants to SP-B levels and newborn lung disease will be determined. The proposed studies will utilize both the Tissue Culture and Clinical Cores

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and involve collaboration with Projects 6, 4 and 7. The new information will provide further understanding of the role of the hydrophobic surfactant proteins in lung development and newborn lung diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T PNEUMONITIS

CELL

ADHESION

MOLECULES

IN

MURINE

LUPUS

Principal Investigator & Institution: Curtis, Jeffrey L.; Professor of Internal Medicine; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2002 Summary: Pulmonary involvement in systemic lupus erythematosus (SLE) is common, often incapacitating, and occasionally lethal. Current therapies are less effective for pulmonary involvement than for other organ systems. To define the molecular pathogenesis of SLE, we have developed a murine model system that depends on adoptive transfer of syngeneic activated CD4+ T cells treated with DNA methyltransferase (DNA MTase) inhibitors such as procainamide (Pca). Normal AKR mice receiving cells of the cloned T cell line D10 that have been treated with Pca (D10Pca) develop high-titer anti-DNA autoantibodies, nephritis, liver disease resembling biliary cirrhosis, and lymphoid interstitial pneumonitis (LIP). Splenectomy abrogates disease activity in all organs except the lungs, indicating that pathology in this organ does not depend of autoantibody production. Treatment with DNA MTase inhibitors increases expression of the Beta2 integrin LFA-1 (CD11a/CD18). T cells transfected with CD18 are also autoreactive and induce lupus on transfer to syngeneic mice. Lymphocyte DNA hypo-methylation and LFA-1 over-expression is also seen in patients with active lupus. These findings imply that T cell overexpression of LFA-1 is sufficient to initiate SLE, and that the T cell-dependent lung lesion may be the earliest stage in the process. This proposal will examine the molecular mechanisms involved in lung pathology in this model system, utilizing a variety of techniques and lessons learned from the study of other models of lung lymphocyte trafficking. Central Hypothesis: Increased LFA-1 expression by autoreactive T cells mediates adhesion both to lung endothelial cells and to lung antigen-presenting cells (APCs), especially macrophages (Mphis) (resulting in apoptosis and release of autoantigens). These interactions initiate recruitment of other activated T cells to the lung via VLA-4/VCAM and selectin-dependent interactions, inducing LIP. Specific Aim 1: To verify the lung localization of D10Pca is required to induce drug-induced murine LIP. Specific Aim 2: To determine the adhesive interactions mediating lung localization of D10Pca and other lung lymphocytes during development of LIP. Specific Aim 3: To determine whether inhibiting pulmonary retention of D10Pca via monoclonal antibody (mAb) treatment prevents development of LIP. Our long-term goal is to develop effective therapies to treat established SLE based on anti-adhesive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF ALPHA-DEFENSINS IN CYSTIC FIBROSIS LUNG DISE Principal Investigator & Institution: Spencer, L T.; Pediatrics; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2001; Project Start 05-JAN-2000; Project End 31-DEC-2004

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Summary: As the principal investigator of this K23 proposal, I will complete fellowship training in pediatric pulmonology at the University of Florida in June 1999. I have accepted a faculty position in the same division effective in July 1999. Having completed 3 years of full-time research in basic and applied sciences in addition to residency and accelerated clinical and research fellowship training, my immediate career goals are to pursue further training in methodology designed to translate investigative findings of biomedical research to clinically useful applications. The proposed training program consists of an early period of relevant didactic training and initiation of research efforts, and culminates in 3 years of mentored research at 80 percent effort. The skills and experience obtained during this 5 year training program will provide opportunities for further research and funding in an independent manner. The proposed research is designed to characterize the role of neutrophil or alpha-defensins in cystic fibrosis (CF) lung disease. Our preliminary data indicates that alpha-defensin levels are significantly elevated in the airways of CF patients compared to healthy volunteers. These peptides possess cytotoxic and inflammatory properties, and may play a role in chronic endobronchial infection in CF. Using bronchoscopic evaluation of the lungs and bronchoalveolar lavage, we plan to define the specific and net effect of alpha-defensins in CF lung disease. We also plan to explore the possibility of modulation of deleterious effects of alpha-defensin with aerosolized alpha1- antitypsin, a molecule that may possess a wide range of therapeutic properties in CF lung disease. The methodology of this project is diverse, consisting of patient selection and recruitment, research bronchoscopy and specimen processing, complimentary ex vivo assays and experiments, collection of clinical data, clinical trial design and administration, and a broad range of statistical analysis methods. Structured didactic training will complement this project in providing multidisciplinary training geared towards independence in the conductance of patient-oriented research. Following completion of this training and research, my long-term career interest will remain in the area of pathogenesis and applied clinical intervention of neutrophil-mediated pulmonary disease in pediatric patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF PECAM IN MODELS OF LUNG INJURY Principal Investigator & Institution: Albelda, Steven M.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1, CD31) is an adhesion and signaling molecule that is expressed on endothelial cells (EC), leukocytes, and platelets. It is a key molecule in regulating transendothelial migration of leukocytes, however little in known about the mechanisms involved or its role in lung disease, despite high levels of expression in the pulmonary circulation. Using PECAM-1 knockout (KO) mice, the investigators have found that lung neutrophil infiltration in immune complex deposition disease is highly PECAMdependent. The goals of this grant are to define the mechanisms by which PECAM regulates transmigration using in vivo and in vitro models and to define the role of PECAM-1 in other models of lung disease. The hypotheses to be tested are that PECAM regulates transmigration through endothelial and neutrophil signaling events mediated by localized regions of the PECAM cytoplasmic domain and that PECAM-1 will play an important role in only specific types of lung injury. Three independent, but related specific aims are proposed: In Aim 1, the mechanisms by which PECAM-1 regulates migration of neutrophils into the lung will be determined using bone marrow chimeras

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generated between wild type and KO animals and by reconstituting PECAM KO mice with specific PECAM-1 isoforms that have mutations in their cytoplasmic domains. In Aim 2, the mechanisms by which PECAM-1 regulates transendothelial migration will be defined using in vitro systems that include a human lung EC transmigration model and experimental transmigration models in which mutant forms of PECAM-1 will be transfected into a PECAM-negative human endothelial-like cell line or into PECAMnegative murine EC's derived from the KO mice. In Aim 3, anti-PECAM-1 antibodies and PECAM knockout mice will be used to test the importance of PECAM-1 in regulating leukocyte transmigration into the lung in "endothelial-driven" vs. "leukocytedriven" lung inflammation, in models of oxidant-induced lung injury, and in other immune-mediated lung injury models. These studies will fill a gap in the basic understanding of lung and cell adhesion biology, as well as provide potentially useful therapeutic information. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF SURFACTANT PROTEIN GENETIC VARIANTS IN CF Principal Investigator & Institution: Floros, Joanna; Associate Professor; Cellular/Molecular Physiology; Pennsylvania State Univ Hershey Med Ctr 500 University Dr Hershey, Pa 17033 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Our long-term objectives are to study mechanisms by which modifier genes affect pulmonary disease severity in patients with cystic fibrosis (CF), with emphasis on the surfactant proteins (SP-), which are produced by lung epithelial cells. SP-A and SP-D play a role in the innate host defense and/or the regulation of inflammatory processes in the lung, and SP-B is essential for normal lung function. Preliminary findings indicate that SP-A genetic variants are associated with disease severity in CF. The overall rationale for the proposed studies is that significant heterogeneity exists in the severity of pulmonary disease in CF patients, even in those that are homozygous for the F508 mutation of the CF transmembrane conductance regulator gene (CFTR). This phenotypic diversity may be related to the genetic heterogeneity of the surfactant protein genes. Genetic variation in the SP-B gene may relate to differences in pulmonary function and genetic variation in SP-A and SP-D may relate to differences in innate host defense function in CF. The overall hypothesis states that SP-A, SP-B, and SP-D are modifiers of pulmonary disease severity in CF and that differences exist among SP-A genetic variants in their ability to modulate phagocytosis of Pseudomonas aeruginosa. In this proposal, we will carry out two major groups of experiments. First, we will study family-based associations by carrying out extended transmission disequilibrium test (ETDT) and/or TDT analyses, of the SP-A, SP-B, and SP-D marker loci, and CF, to determine whether these loci are linked to CF and identify susceptibility SP alleles for CF severity. The entire CF study group as well as a number of subgroups based on CFTR genotype, severity, or other criteria, will be studied. Logistic regression analysis will be used to identify factors that may be of particular significance in CF along with specific genotypes (Aim 1). In the second group of experiments, we will focus on SP-A genetic variants for which preliminary evidence of an association between SP-A alleles and CF severity exists. We will study differences in the ability of SP-A alleles to enhance phagocytosis, by a macrophage-like cell line, of laboratory strains of mucoid and non-mucoid P. aeruginosa grown under different environmental conditions that have been shown to reproduce certain biochemical and functional characteristics found in clinical isolates of P. aeruginosa (Aim 2) and of mucoid and non-mucoid isolates of P. aeruginosa from CF patients (Aim 3). The

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findings may help identify specific host defense mechanisms involving alleles associated with pulmonary disease severity in CF and develop a useful in vitro model to study the in vivo modifications of P. aeruginosa and its clearance, and provide the basis for further consideration of novel therapeutic strategies to treat CF-related lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TLR'S, NITRIC OXIDE AND CHRONIC LUNG DISEASE Principal Investigator & Institution: Truog, William E.; Professor; Children's Mercy Hosp (Kansas City, Mo) 2401 Gillham Rd Kansas City, Mo 64108 Timing: Fiscal Year 2002; Project Start 10-FEB-2002; Project End 31-JAN-2006 Summary: (provided by applicant): This application is submitted in response to RFA Hl00-012: Ancillary Studies in Lung Disease Trials. The parent trial to which this application is linked, (U01-HL62514), is testing the hypothesis that low dose inhaled nitric oxide, administered to infants 500 to 1250 g birth weight, will produce an increase in survival without chronic lung disease (CLD) from 50 percent to 61 percent at 36 week post menstrual age. The parent study is a blinded, placebo controlled, three week trial of decreasing dose nitric oxide or placebo beginning between 7 and 21 days of age. Part of the rationale supporting the parent trial is that nitric oxide may moderate pulmonary inflammation, a crucial precursor of full-blown CLD. Although the parent trial includes measurements of tracheal aspirate interleukin 1B and interleukin-8, it cannot investigate mechanisms of, nor initiation, propagation, or persistence of, pulmonary inflammation. Our proposed study will examine the role of two members of the family of transmembrane receptors, Toll-like receptors (TLRs), found on leukocytes and other cells and upregulated in response to endotoxin and to other stimuli. These substances transduce the signal propagating inflammatory mediator production. We will quantitate protein expression and mRNA expression of TLR-2, and TLR-4 from leukocytes obtained from serial tracheal aspirate samples. We will perform these serial studies in a subset of enrolled patients who will mirror the parent clinical trial sample in terms of ethnicity, gender, and severity of underlying disease. Our specific aims are to determine if upregulation of TLR-2 and/or TLR-4 antedates development of CLD of prematurity and to determine if there is a significant correlation with severity of CLD. We will determine if the mechanism of improved outcome with NO administration occurs in association with NO-associated suppression of upregulation of TLR, a possibility for which we have supportive pilot data. Even if the parent study cannot reject the null hypothesis that nitric oxide will have no benefit in this disease, this mechanistic study will provide important new information about natural history of CLD and about crucial mechanisms of early pulmonary inflammation. Its results may also open up intriguing pathways for treatments aimed at selective diminution of pulmonary inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSLATIONAL RESEARCH IN LUNG BIOLOGY AND DISEASE Principal Investigator & Institution: Irvin, Charles G.; Professor of Medicine; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Lung disease is a significant cause of mortality and morbidity in the United States. While all other major causes of death are decreasing, age- adjusted mortality due to lung disease continues to rise. The overall purpose of this COBRE application si to develop a research program in the lung biology and disease at The Vermont Lung Center (VLC) in which 5 promising young scientists can translate basic laboratory

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research into clinical applications, while developing into independent investigators. 1) Train and mentor a group of talented MD and PhD biomedical investigators 2) Provide career development and guidance with skilled mentoring. 3) Create a stimulating, supportive and "cutting edge" research milieu. As support for these endeavors, we will also develop a state-of-the-art transgenic animal facility and augment the biomedical engineering research program at The University of Vermont. The VLC-COBRE will undertake 5 separate, but inter-related, research projects with the following aims: 1) to understand the mechanisms of the lung periphery of the lung periphery and its derangement in asthma, 2) to determine the mechanism by which proteolysis causes inflammation and its role in the pathogenesis of asthma, and 4) to ascertain the nature of the mechanical load applied to the pulmonary vasculature and the mechanisms causing structural remodeling. This proposal addresses the urgent need to expand and support translational research, because translational research concerts advances in molecular, cellular and genetic science into new methods of diagnosis and therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT DECISIONS IN ADVANCED GENETIC LUNG DISEASE Principal Investigator & Institution: Mcinnes, Susan; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2004 Summary: (Provided by the Applicant) Individuals with cystic fibrosis (CF) and alpha 1antitrypsin (AAT) deficiency pulmonary disease face many difficult decisions throughout the course of their lives and illnesses. The events culminating in these events may be called Milestone Life Events (MLEs). Decisions regarding goals of care in patients with advanced disease are particularly onerous. Two such MLEs may include the decision whether or not to pursue lung transplantation, and decisions about advance care planning for the end of life. Patients may not be prepared adequately to face these MLEs and, therefore, may struggle with these decisions. This study seeks to investigate these MLEs and the decision-making issues related to them for patients with advanced CF and AAT pulmonary disease. The specific aims of this study are to: 1) identify ways to increase patient comfort with making treatment-related decisions, 2) identify the beliefs and understanding of patients about decisions regarding lung transplantation and advance care planning, 3) identify key issues for patients' informational needs around treatment decisions, 4) determine if patient-defined informational needs are expected by clinicians caring for those patients, and 5) plan for development of a survey instrument for a larger population of patients with CF and AAT in order to develop educational material and specific advance directive forms. This exploratory study will utilize the qualitative research tool of focus group interviewing to generate rich descriptive data about these issues. Adult patients with CF and AAT who are seen at sub-specialty CF and AAT clinics will be invited to participate in a focus group. Three focus groups of each disease-specific population will convene. The data will be analyzed by an iterative process to ensure reliability, then further investigations will be planned to develop a survey tool, and eventually educational materials and resources for patients facing these MLEs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: V & Q DISTURBANCES IN OBLITERATIVE BRONCHIOLITIS Principal Investigator & Institution: Lipson, David A.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104

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Timing: Fiscal Year 2001; Project Start 06-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Candidate?s Plans/Training: The candidate plans a career as an independent clinical investigator focusing on patient oriented research related to advanced lung disease and lung transplantation. Training will include formal epidemiological course work in patient oriented research, a mentored laboratory experience, and closely mentored completion of the research protocol. Environment: The University of Pennsylvania is a uniquely suited environment for this training award. The Center for Clinical Epidemiology and Biostatistics will provide formal didactic training. The Metabolic Magnetic Resonance Research and Computing Center will provide a mentored laboratory experience. Research: Obliterative Bronchiolitis (OB) is recognized as a form of chronic allograft rejection and affects as many as 60 to 80% of lung transplant recipients between 5 and 10 years after transplantation. Diagnosis of OB is difficult to make, yet detection of the disease is important because patients who have OB detected early may have improved survival. Current techniques in detection include lung biopsy, which is insensitive and morbid, and spirometry, which detects disease after it has progressed. Recently, non-invasive functional MRI methods using hyperpolarized, non-radioactive 3He gas and magnetic labeling of blood, termed "Arterial Spin-Tagging" (AST) have been developed which detect ventilation and perfusion (V & Q) disturbances in patients with airway obstruction, such as in OB. The overall hypothesis of the proposal is that a predictive model combining clinical risk factors for OB with the detection of airspace and perfusion disturbances using 3He and AST MR imaging will identify OB earlier than conventional techniques. The study has three specific aims: (1) a retrospective cohort study to examine the relationship between clinical parameters and the incidence of OB; (2) a prospective cohort study to test the hypothesis that V & Q imaging using hyperpolarized 3He and AST MRI can differentiate between normal subjects and patients with varying degrees of airway obstruction and (3) a prospective cohort study to test the hypothesis that V & Q as visualized by 3He and AST MRI following lung transplant predicts patients who will develop OB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VENTILATOR-INDUCED LUNG INJURY IN CHILDREN Principal Investigator & Institution: Heidemann, Sabrina Marie.; Pediatrics; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): The long-term goal of this research project is to develop ventilator strategies that will minimize lung damage in children thus leading to a decrease in mortality and chronic lung injury. The objective of this R21 application is to compare the extent of lung injury in children with two different ventilator strategies: pressure control and volume control ventilation. The central hypothesis for the proposed research is that compared to volume control, pressure control ventilation causes increased lung damage. Evidence of lung damage will be assessed by increase in oxygenation indices. Increase in concentrations of the pro-inflammatory cytokines tumor necrosis factor alpha, interleukin-6, and interleukin-8 will be used as indicators of injury. We have formulated this hypothesis based on strong preliminary findings from pre-clinical data in rats with acute lung injury. These data demonstrate that pressure control ventilation is associated with higher oxygenation indices and increased production of the pro-inflammatory mediators, specifically; tumor necrosis factor, cytokine-induced neutrophil chemoattractant and macrophage inflammatory protein-2. The rationale for the proposed research is that human pediatric studies are essential to

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provide a rational basis for selection of ventilation mode for treatment of children with acute lung injury. In this pilot study, children with and without chronic lung disease who develop respiratory failure from acute lung injury will be randomized to receive either pressure or volume control ventilation. Children with chronic lung disease will be studied separately from children with no previous lung disease. Oxygenation indices and pro-inflammatory cytokine concentrations of tumor necrosis factor alpha, interleukin-6, and interleukin-8 will be measured daily in the blood and lung lavage fluid for the first three days of mechanical ventilation. Specific aim 1 will compare the change in oxygenation index during the three-day period in children with acute lung injury by ventilator mode: pressure or volume control. Specific aim 2 will determine the change in pro-inflammatory cytokine concentrations during the three-day period in children with acute lung injury receiving pressure control or volume control ventilation. The proposed research will provide data critical to the understanding of ventilatorinduced lung injury in children with and without chronic lung disease. The results of this study may serve as the basis for a multicenter clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “lung disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lung disease in the PubMed Central database: •

Angiogenesis in the pathogenesis of inflammatory joint and lung diseases. by Walsh DA, Pearson CI.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128891

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C5a anaphylatoxin is a major regulator of activating versus inhibitory Fc[gamma]Rs in immune complex --induced lung disease. by Shushakova N, Skokowa J, Schulman J, Baumann U, Zwirner J, Schmidt RE, Gessner JE.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151656

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Immune Response to Haemophilus parainfluenzae in Patients with Chronic Obstructive Lung Disease. by Mitchell JL, Hill SL.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95817

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In Vivo Penicillin MIC Drift to Extremely High Resistance in Serotype 14 Streptococcus pneumoniae Persistently Colonizing the Nasopharynx of an Infant with Chronic Suppurative Lung Disease: a Case Study. by Leach AJ, Morris PS, SmithVaughan H, Mathews JD.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128758

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Molecular Epidemiology of Scedosporium apiospermum Infection Determined by PCR Amplification of Ribosomal Intergenic Spacer Sequences in Patients with Chronic Lung Disease. by Williamson EC, Speers D, Arthur IH, Harnett G, Ryan G, Inglis TJ.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87677

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Role of endothelin-1 in lung disease. by Fagan KA, McMurtry IF, Rodman DM.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59574

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The Pseudomonas aeruginosa Secretory Product Pyocyanin Inactivates [alpha]1 Protease Inhibitor: Implications for the Pathogenesis of Cystic Fibrosis Lung Disease. by Britigan BE, Railsback MA, Cox CD.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96448

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with lung disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “lung disease” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for lung disease (hyperlinks lead to article summaries): •

A 56-year-old woman with mixed obstructive and restrictive lung disease. Author(s): Khan SU, Kavuru MS. Source: Respiratory Care. 2000 May; 45(5): 533-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10813230&dopt=Abstract

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A risk-benefit assessment of drugs used for neonatal chronic lung disease. Author(s): Sweet DG, Halliday HL. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 2000 May; 22(5): 389-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10830255&dopt=Abstract

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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Abnormal expression of surfactant protein C and lung disease. Author(s): Nogee LM. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 June; 26(6): 641-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034561&dopt=Abstract

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Acute parenchymal lung disease in immunocompetent patients: diagnostic accuracy of high-resolution CT. Author(s): Tomiyama N, Muller NL, Johkoh T, Honda O, Mihara N, Kozuka T, Hamada S, Nakamura H, Akira M, Ichikado K. Source: Ajr. American Journal of Roentgenology. 2000 June; 174(6): 1745-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10845517&dopt=Abstract

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Adrenocortical function and chronic lung disease of pre-maturity: an unresolved problem? Author(s): Romagnoli C, Latella C, Zecca E, Papacci P, Tortorolo G. Source: J Endocrinol Invest. 2002 October; 25(9): 759-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398232&dopt=Abstract

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Aeolus myth: chronic obstructive lung disease and nocturnal lumbosacral pain in association with lumbar spinal stenosis and pulmonary hypertension. Author(s): LaBan MM, Kucway EJ. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 September; 82(9): 660-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12960906&dopt=Abstract

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Agricultural lung disease. Author(s): Spurzem JR, Romberger DJ, Von Essen SG. Source: Clinics in Chest Medicine. 2002 December; 23(4): 795-810. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512166&dopt=Abstract

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Airway remodelling in chronic lung disease of prematurity. Author(s): Sweet DG, Halliday HL, Warner JA. Source: Paediatric Respiratory Reviews. 2002 June; 3(2): 140-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297062&dopt=Abstract

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Allogeneic stem cell transplant, lung disease, and airflow obstruction. Author(s): Folz RJ. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 146-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851243&dopt=Abstract

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Alpha 1-antitrypsin deficiency alleles in cystic fibrosis lung disease. Author(s): Frangolias DD, Ruan J, Wilcox PJ, Davidson AG, Wong LT, Berthiaume Y, Hennessey R, Freitag A, Pedder L, Corey M, Sweezey N, Zielenski J, Tullis E, Sandford AJ. Source: American Journal of Respiratory Cell and Molecular Biology. 2003 September; 29(3 Pt 1): 390-6. Epub 2003 April 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689922&dopt=Abstract

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Altered fatty acid composition of lung surfactant phospholipids in interstitial lung disease. Author(s): Schmidt R, Meier U, Markart P, Grimminger F, Velcovsky HG, Morr H, Seeger W, Gunther A. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2002 November; 283(5): L1079-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376361&dopt=Abstract

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An overview of the pathogenesis of cystic fibrosis lung disease. Author(s): Boucher RC. Source: Advanced Drug Delivery Reviews. 2002 December 5; 54(11): 1359-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458149&dopt=Abstract

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Annual lung function changes in young patients with chronic lung disease. Author(s): Merkus PJ, Tiddens HA, de Jongste JC. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 May; 19(5): 886-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030729&dopt=Abstract

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Antenatal glucocorticoid treatment increases the rate of “survival without chronic lung disease” among 25- to 29-week preterm infants. Author(s): Figueras-Aloy J, Krauel X, Carbonell X. Source: The Journal of Pediatrics. 2002 April; 140(4): 486-7; Author Reply 487. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006971&dopt=Abstract

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Antenatal inflammation and infection in chronic lung disease of prematurity. Author(s): Miralles RE, Hodge R, Kotecha S. Source: Child: Care, Health and Development. 2002 September; 28 Suppl 1: 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515431&dopt=Abstract

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Anti Jo-1 myositis. 'Mechanic's hands' and interstitial lung disease. Author(s): Taggart AJ, Finch MB, Courtney PA, Gormley GJ. Source: Ulster Med J. 2002 May; 71(1): 68-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137171&dopt=Abstract

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Arterial endothelin-1 in interstitial lung disease patients with pulmonary hypertension. Author(s): Trakada G, Spiropoulos K. Source: Monaldi Arch Chest Dis. 2001 October; 56(5): 379-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887493&dopt=Abstract

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Assessing occupational and environmental exposures that cause lung disease. Author(s): Bracker A, Storey E. Source: Clinics in Chest Medicine. 2002 December; 23(4): 695-705. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512159&dopt=Abstract

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Assessing oxygen requirement after discharge in chronic lung disease: a survey of current practice. Author(s): Solis A, Harrison G, Shaw BN. Source: European Journal of Pediatrics. 2002 August; 161(8): 428-30. Epub 2002 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172825&dopt=Abstract

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Association between myocardial right ventricular relaxation time and pulmonary arterial pressure in chronic obstructive lung disease: analysis by pulsed Doppler tissue imaging. Author(s): Caso P, Galderisi M, Cicala S, Cioppa C, D'Andrea A, Lagioia G, Liccardo B, Martiniello AR, Mininni N. Source: Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. 2001 October; 14(10): 970-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11593201&dopt=Abstract

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BAL fluid cytology in the assessment of infectious lung disease. Author(s): Jacobs JA, De Brauwer E. Source: Hosp Med. 1999 August; 60(8): 550-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10621807&dopt=Abstract

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Barotrauma, oxygen toxicity, and chronic lung disease. Author(s): Mammel MC, deRegnier RA. Source: Pediatrics. 2001 August; 108(2): 525. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491120&dopt=Abstract

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Bayesian inference for a generalized population attributable fraction: the impact of early vitamin A levels on chronic lung disease in very low birthweight infants. Author(s): Graham P. Source: Statistics in Medicine. 2000 April 15; 19(7): 937-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10750061&dopt=Abstract

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Beryllium-induced lung disease. Author(s): Brooks MH. Source: Isr Med Assoc J. 2001 September; 3(9): 711. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574997&dopt=Abstract

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beta2 adrenoceptor gene polymorphisms in cystic fibrosis lung disease. Author(s): Buscher R, Eilmes KJ, Grasemann H, Torres B, Knauer N, Sroka K, Insel PA, Ratjen F. Source: Pharmacogenetics. 2002 July; 12(5): 347-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142724&dopt=Abstract

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Bilateral lung transplant: the procedure of choice for end-stage septic lung disease. Author(s): Rao JN, Forty J, Hasan A, Hilton CJ, Ledingham S, Parry G, Wardle J, Gould FK, Corris PA, Dark JH. Source: Transplantation Proceedings. 2001 February-March; 33(1-2): 1622-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11267445&dopt=Abstract

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Blocking leukocyte influx and function to prevent chronic lung disease of prematurity. Author(s): Auten RL, Ekekezie II. Source: Pediatric Pulmonology. 2003 May; 35(5): 335-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687589&dopt=Abstract

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Body composition in infants with chronic lung disease after treatment with dexamethasone. Author(s): Bolt RJ, van Weissenbruch MM, Roos JC, Delemarre-van de Waal HA, Cranendonk A, Lafeber HN. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(7): 815-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200909&dopt=Abstract

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Body composition of children with chronic lung disease. Author(s): Dumas C, Skaff C, Just J, Tounian P, Fontaine JL, Grimfeld A, Girardet JP. Source: Pediatr Pulmonol Suppl. 1997; 16: 174-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443260&dopt=Abstract

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Bone mass and vitamin D deficiency in adults with advanced cystic fibrosis lung disease. Author(s): Donovan DS Jr, Papadopoulos A, Staron RB, Addesso V, Schulman L, McGregor C, Cosman F, Lindsay RL, Shane E. Source: American Journal of Respiratory and Critical Care Medicine. 1998 June; 157(6 Pt 1): 1892-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9620924&dopt=Abstract

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Branched-chain aminoacids and retraining of patients with chronic obstructive lung disease. Author(s): Menier R, Talmud J, Laplaud D, Bernard MP. Source: The Journal of Sports Medicine and Physical Fitness. 2001 December; 41(4): 5004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687770&dopt=Abstract

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Bronchiectasis: the 'other' obstructive lung disease. Author(s): Mysliwiec V, Pina JS. Source: Postgraduate Medicine. 1999 July; 106(1): 123-6, 128-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10418580&dopt=Abstract

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Bronchoalveolar inflammation following airway infection in preterm infants with chronic lung disease. Author(s): Groneck P, Schmale J, Soditt V, Stutzer H, Gotze-Speer B, Speer CP. Source: Pediatric Pulmonology. 2001 May; 31(5): 331-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11340678&dopt=Abstract

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Bronchoalveolar lavage in children with chronic diffuse parenchymal lung disease. Author(s): Ronchetti R, Midulla F, Sandstrom T, Bjermer L, Zebrak J, Pawlik J, Villa MP, Villani A. Source: Pediatric Pulmonology. 1999 June; 27(6): 395-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10380091&dopt=Abstract

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Bronchoalveolar lavage in interstitial lung disease. Author(s): Costabel U, Guzman J. Source: Current Opinion in Pulmonary Medicine. 2001 September; 7(5): 255-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584173&dopt=Abstract

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Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants. Author(s): Ng GY, da S, Ohlsson A. Source: Cochrane Database Syst Rev. 2001; (3): Cd003214. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687053&dopt=Abstract

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Bronchopulmonary dysplasia (chronic lung disease of infancy): an update for the pediatrician. Author(s): Nievas FF, Chernick V. Source: Clinical Pediatrics. 2002 March; 41(2): 77-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931335&dopt=Abstract

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Bronchopulmonary dysplasia and chronic lung disease of infancy: strategies for prevention and management. Author(s): Ho LY. Source: Ann Acad Med Singapore. 2002 January; 31(1): 119-30; Quiz 131. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885487&dopt=Abstract

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Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease. Author(s): Chang AB, Boyce NC, Masters IB, Torzillo PJ, Masel JP. Source: Thorax. 2002 November; 57(11): 935-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403874&dopt=Abstract

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Budesonide delivered by dosimetric jet nebulization to preterm very low birthweight infants at high risk for development of chronic lung disease. Author(s): Jonsson B, Eriksson M, Soder O, Broberger U, Lagercrantz H. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 December; 89(12): 1449-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11195235&dopt=Abstract

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CA15-3 and cancer associated serum antigen assays are alternatives to the KL-6 assay for measuring serum MUC-1 levels in patients with interstitial lung disease associated with polymyositis/dermatomyositis. Author(s): Wong RC, Klingberg S, Wilson R. Source: The Journal of Rheumatology. 2002 September; 29(9): 2021-2; Author Reply 2022. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233905&dopt=Abstract

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Cerebral oxygenation during exercise in patients with terminal lung disease. Author(s): Jensen G, Nielsen HB, Ide K, Madsen PL, Svendsen LB, Svendsen UG, Secher NH. Source: Chest. 2002 August; 122(2): 445-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171815&dopt=Abstract

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Chorioamnionitis and increased neonatal lung lavage fluid matrix metalloproteinase9 levels: implications for antenatal origins of chronic lung disease. Author(s): Curley AE, Sweet DG, Thornton CM, O'Hara MD, Chesshyre E, Pizzotti J, Wilbourn MS, Halliday HL, Warner JA. Source: American Journal of Obstetrics and Gynecology. 2003 April; 188(4): 871-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712078&dopt=Abstract

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Chronic cystic lung disease: diagnostic accuracy of high-resolution CT in 92 patients. Author(s): Koyama M, Johkoh T, Honda O, Tsubamoto M, Kozuka T, Tomiyama N, Hamada S, Nakamura H, Akira M, Ichikado K, Fujimoto K, Rikimaru T, Tateishi U, Muller NL. Source: Ajr. American Journal of Roentgenology. 2003 March; 180(3): 827-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591705&dopt=Abstract

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Chronic human parvovirus B19 infection associated with interstitial lung disease. Author(s): Klar A, Halamish A, Shoseyov D, Cassinotti P, Siegl G, Springer C, Shazberg G, Hurvitz H. Source: Isr Med Assoc J. 2002 October; 4(10): 825-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389353&dopt=Abstract

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Chronic interstitial lung disease with lung fibrosis in a girl: uncommon sequelae of Epstein-Barr virus infection. Author(s): Ankermann T, Claviez A, Wagner HJ, Krams M, Riedel F. Source: Pediatric Pulmonology. 2003 March; 35(3): 234-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567394&dopt=Abstract

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Chronic lung disease after activated charcoal aspiration. Author(s): Graff GR, Stark J, Berkenbosch JW, Holcomb GW 3rd, Garola RE. Source: Pediatrics. 2002 May; 109(5): 959-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986462&dopt=Abstract

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Chronic lung disease of prematurity and intrauterine growth retardation: a population-based study. Author(s): Lal MK, Manktelow BN, Draper ES, Field DJ; Population-based study. Source: Pediatrics. 2003 March; 111(3): 483-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612225&dopt=Abstract

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Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases. Author(s): Maier LA. Source: Journal of Thoracic Imaging. 2002 October; 17(4): 273-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362066&dopt=Abstract

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Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease. Author(s): Ihn H, Asano Y, Kubo M, Yamane K, Jinnin M, Yazawa N, Fujimoto M, Tamaki K. Source: Rheumatology (Oxford, England). 2002 November; 41(11): 1268-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421999&dopt=Abstract

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CO2 retention in lung disease; could there be a pre-existing difference in respiratory physiology. Author(s): Dunroy HM, Adams L, Corfield DR, Morrell MJ. Source: Respiratory Physiology & Neurobiology. 2003 July 16; 136(2-3): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853009&dopt=Abstract

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Cognitive development at 5.5 years of children with chronic lung disease of prematurity. Author(s): Bohm B, Katz-Salamon M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 March; 88(2): F101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598496&dopt=Abstract

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Collagen scaffolding during development and its deformation with chronic lung disease. Author(s): Thibeault DW, Mabry SM, Ekekezie II, Zhang X, Truog WE. Source: Pediatrics. 2003 April; 111(4 Pt 1): 766-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671110&dopt=Abstract

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Congenital cystic lung disease: diagnostic and therapeutic considerations. Author(s): Horak E, Bodner J, Gassner I, Schmid T, Simma B, Grassl G, Sawyer SM. Source: Clinical Pediatrics. 2003 April; 42(3): 251-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739924&dopt=Abstract

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Controlled trial of early dexamethasone treatment for the prevention of chronic lung disease in preterm infants: a 3-year follow-up. Author(s): Romagnoli C, Zecca E, Luciano R, Torrioli G, Tortorolo G. Source: Pediatrics. 2002 June; 109(6): E85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042579&dopt=Abstract

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Correlation between the numbers of gammadelta T cells and CD4+ HLA-DR+ T cells in broncho-alveolar lavage fluid from patients with diffuse lung disease. Author(s): Suzuki E, Tsukada H, Ishida T, Ishizuka O, Hasegawa T, Gejyo F. Source: The Tohoku Journal of Experimental Medicine. 2002 April; 196(4): 231-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086151&dopt=Abstract

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Cost-of-illness of lung disease in the TriVeneto Region, Italy: the GOLD Study. Author(s): Dal Negro R, Berto P, Tognella S, Quareni L; Global Outcomes in Lung Disease Study Group. Source: Monaldi Arch Chest Dis. 2002 February; 57(1): 3-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174698&dopt=Abstract

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Current perspectives on the prevention and management of chronic lung disease in preterm infants. Author(s): Shah PS. Source: Paediatric Drugs. 2003; 5(7): 463-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837119&dopt=Abstract

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Cyclophosphamide-induced late-onset lung disease. Author(s): Hamada K, Nagai S, Kitaichi M, Jin G, Shigematsu M, Nagao T, Sato A, Mishima M. Source: Intern Med. 2003 January; 42(1): 82-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583625&dopt=Abstract

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Cystic lung disease in Sjogren's syndrome. Author(s): Hubscher O, Re R, Iotti R. Source: The Journal of Rheumatology. 2002 October; 29(10): 2235-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375340&dopt=Abstract

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Decreased neutrophil apoptosis in tracheal fluids of preterm infants at risk of chronic lung disease. Author(s): Oei J, Lui K, Wang H, Henry R. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 May; 88(3): F245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719400&dopt=Abstract

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Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants. Author(s): Halliday HL, Ehrenkranz RA, Doyle LW. Source: Cochrane Database Syst Rev. 2003; (1): Cd001145. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535401&dopt=Abstract

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Development of chronic lung disease in preterm infants treated with surfactant. Author(s): Hammoud MS, Thalib L. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 October; 44(5): 493-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225547&dopt=Abstract

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Dexamethasone therapy in chronic lung disease. Author(s): Sardesai S, Durand M. Source: Indian J Pediatr. 1996 January-February; 63(1): 61-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829966&dopt=Abstract

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Dexamethasone treatment and fluid balance in preterm infants at risk for chronic lung disease. Author(s): Bos AF, van Asselt WA, Okken A. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 May; 89(5): 562-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852193&dopt=Abstract

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Dexamethasone treatment does not inhibit fibroproliferation in chronic lung disease of prematurity. Author(s): Dik WA, Versnel MA, Naber BA, Janssen DJ, van Kaam AH, Zimmermann LJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 May; 21(5): 842-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765431&dopt=Abstract

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Diagnostic approach to the patient with diffuse lung disease. Author(s): Ryu JH, Olson EJ, Midthun DE, Swensen SJ. Source: Mayo Clinic Proceedings. 2002 November; 77(11): 1221-7; Quiz 1227. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440558&dopt=Abstract

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Different sensitization profile for asthma, rhinitis, and eczema among 7-8-year-old children: report from the Obstructive Lung Disease in Northern Sweden studies. Author(s): Ronmark E, Perzanowski M, Platts-Mills T, Lundback B. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2003 April; 14(2): 91-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675754&dopt=Abstract

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Differential diagnosis in chronic diffuse infiltrative lung disease on high-resolution computed tomography. Author(s): Screaton NJ, Hiorns MP, Muller NL. Source: Semin Roentgenol. 2002 January; 37(1): 17-24. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987762&dopt=Abstract

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Diffuse infiltrative lung disease associated with flecainide. Report of two cases. Author(s): Pesenti S, Lauque D, Daste G, Boulay V, Pujazon MC, Carles P. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(2): 182-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961436&dopt=Abstract

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Diffuse lung disease in the immunocompromised non-HIV patient. Author(s): Gosselin MV. Source: Semin Roentgenol. 2002 January; 37(1): 37-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987765&dopt=Abstract

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Diffuse parenchymal lung disease (DPLD). Author(s): Johnston I. Source: Nurs Times. 2001 March 22-28; 97(12): Ii-Iv. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954410&dopt=Abstract

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Diffuse parenchymal lung disease: an approach to diagnosis. Author(s): Mahajan R, Daga MK, Tiwari N. Source: J Assoc Physicians India. 2002 October; 50: 1285-94. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568216&dopt=Abstract

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Direct and indirect immunofluorescence as a diagnostic adjunct in the interpretation of nonneoplastic medical lung disease. Author(s): Magro CM, Morrison C, Pope-Harman A, Rothrauff SK, Ross P Jr. Source: American Journal of Clinical Pathology. 2003 February; 119(2): 279-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580000&dopt=Abstract

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Diuretics acting on the distal renal tubule for preterm infants with (or developing) chronic lung disease. Author(s): Brion LP, Primhak RA, Ambrosio-Perez I. Source: Cochrane Database Syst Rev. 2000; (3): Cd001817. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908511&dopt=Abstract

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Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network. Author(s): Van Marter LJ, Allred EN, Pagano M, Sanocka U, Parad R, Moore M, Susser M, Paneth N, Leviton A. Source: Pediatrics. 2000 June; 105(6): 1194-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10835057&dopt=Abstract

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Does lung biopsy help patients with interstitial lung disease? Author(s): Qureshi RA, Ahmed TA, Grayson AD, Soorae AS, Drakeley MJ, Page RD. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 April; 21(4): 621-6; Discussion 626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932157&dopt=Abstract

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Dornase alfa in early cystic fibrosis lung disease. Author(s): Robinson PJ. Source: Pediatric Pulmonology. 2002 September; 34(3): 237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203856&dopt=Abstract

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Drug-induced lung disease: high-resolution CT and histological findings. Author(s): Cleverley JR, Screaton NJ, Hiorns MP, Flint JD, Muller NL. Source: Clinical Radiology. 2002 April; 57(4): 292-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014876&dopt=Abstract

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Dyspnea and decreased variability of breathing in patients with restrictive lung disease. Author(s): Brack T, Jubran A, Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2002 May 1; 165(9): 1260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991875&dopt=Abstract

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Early infection and progression of cystic fibrosis lung disease. Author(s): Koch C. Source: Pediatric Pulmonology. 2002 September; 34(3): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203855&dopt=Abstract

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Early motor and mental development in very preterm infants with chronic lung disease. Author(s): Katz-Salamon M, Gerner EM, Jonsson B, Lagercrantz H. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2000 July; 83(1): F1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873161&dopt=Abstract

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Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants. Author(s): Halliday HL, Ehrenkranz RA, Doyle LW. Source: Cochrane Database Syst Rev. 2003; (1): Cd001146. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535402&dopt=Abstract

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Early respiratory system mechanics and the prediction of chronic lung disease in ventilated preterm neonates requiring surfactant treatment. Author(s): Choukroun ML, Tayara N, Fayon M, Demarquez JL. Source: Biology of the Neonate. 2003; 83(1): 30-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566681&dopt=Abstract

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Effect of hypobaric hypoxia on blood gases in patients with restrictive lung disease. Author(s): Christensen CC, Ryg MS, Refvem OK, Skjonsberg OH. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 August; 20(2): 300-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12212959&dopt=Abstract

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Effect of once weekly pulmonary rehabilitation on exercise tolerance in patients with chronic lung disease. Author(s): O'Neill BM, Johnston D, Burrell N, MacMahon J. Source: Ir J Med Sci. 2001 October-December; 170(4): 231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918326&dopt=Abstract

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Effects of dexamethasone treatment on bone and collagen turnover in preterm infants with chronic lung disease. Author(s): Crofton PM, Shrivastava A, Wade JC, Stephen R, Kelnar CJH, Mcintosh N, Lyon AJ. Source: Pediatric Research. 2000 August; 48(2): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10926289&dopt=Abstract

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Elevated levels of leukotriene B4 and leukotriene E4 in bronchoalveolar lavage fluid from patients with scleroderma lung disease. Author(s): Kowal-Bielecka O, Distler O, Kowal K, Siergiejko Z, Chwiecko J, Sulik A, Gay RE, Lukaszyk AB, Gay S, Sierakowski S. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1639-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794832&dopt=Abstract

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Endothelial nitric oxide synthase variants in cystic fibrosis lung disease. Author(s): Grasemann H, van's Gravesande KS, Buscher R, Knauer N, Silverman ES, Palmer LJ, Drazen JM, Ratjen F. Source: American Journal of Respiratory and Critical Care Medicine. 2003 February 1; 167(3): 390-4. Epub 2002 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406848&dopt=Abstract

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Energy expenditure and plasma catecholamines in preterm infants with mild chronic lung disease. Author(s): Bauer J, Maier K, Muehlbauer B, Poeschl J, Linderkamp O. Source: Early Human Development. 2003 June; 72(2): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782426&dopt=Abstract

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Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease. Author(s): Gunther A, Mosavi P, Ruppert C, Heinemann S, Temmesfeld B, Velcovsky HG, Morr H, Grimminger F, Walmrath D, Seeger W. Source: Thrombosis and Haemostasis. 2000 June; 83(6): 853-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896238&dopt=Abstract

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Environmental and genetic risk factors and gene-environment interactions in the pathogenesis of chronic obstructive lung disease. Author(s): Walter R, Gottlieb DJ, O'Connor GT. Source: Environmental Health Perspectives. 2000 August; 108 Suppl 4: 733-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10931792&dopt=Abstract

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Eosinophilic lung disease in the tropics. Author(s): Savani DM, Sharma OP. Source: Clinics in Chest Medicine. 2002 June; 23(2): 377-96, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092033&dopt=Abstract

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Eosinophilic lung disease under chemotherapy with oxaliplatin for colorectal cancer. Author(s): Gagnadoux F, Roiron C, Carrie E, Monnier-Cholley L, Lebeau B. Source: American Journal of Clinical Oncology : the Official Publication of the American Radium Society. 2002 August; 25(4): 388-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151971&dopt=Abstract

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Ethics and decision making in end stage lung disease. Author(s): Simonds AK. Source: Thorax. 2003 March; 58(3): 272-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612311&dopt=Abstract

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European framework for tuberculosis control and elimination in countries with a low incidence. Recommendations of the World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Royal Netherlands Tuberculosis Association (KNCV) Working Group. Author(s): Broekmans JF, Migliori GB, Rieder HL, Lees J, Ruutu P, Loddenkemper R, Raviglione MC; World Health Organization, International Union Against Tuberculosis and Lung Disease, and Royal Netherlands Tuberculosis Association Working Group. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 April; 19(4): 765-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999007&dopt=Abstract

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Evaluation and development of potentially better practices to prevent chronic lung disease and reduce lung injury in neonates. Author(s): Sharek PJ, Baker R, Litman F, Kaempf J, Burch K, Schwarz E, Sun S, Payne NR. Source: Pediatrics. 2003 April; 111(4 Pt 2): E426-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671162&dopt=Abstract

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Exhaled breath condensate: an evolving tool for noninvasive evaluation of lung disease. Author(s): Hunt J. Source: The Journal of Allergy and Clinical Immunology. 2002 July; 110(1): 28-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110814&dopt=Abstract

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Exhaled carbon monoxide in lung disease. Author(s): Paredi P, Kharitonov SA, Barnes PJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 January; 21(1): 197; Author Reply 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570130&dopt=Abstract

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Exhaled nitric oxide at school age in prematurely born infants with neonatal chronic lung disease. Author(s): Mieskonen ST, Malmberg LP, Kari MA, Pelkonen AS, Turpeinen MT, Hallman NM, Sovijarvi AR. Source: Pediatric Pulmonology. 2002 May; 33(5): 347-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11948979&dopt=Abstract

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Factors affecting the incidence of chronic lung disease of prematurity in 1987, 1992, and 1997. Author(s): Manktelow BN, Draper ES, Annamalai S, Field D. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2001 July; 85(1): F33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11420319&dopt=Abstract

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Factors in creating sustainable intersectoral community mobilization for prevention of heart and lung disease. Author(s): Bourdages J, Sauvageau L, Lepage C. Source: Health Promotion International. 2003 June; 18(2): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746385&dopt=Abstract

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Factors influencing survival in children with chronic interstitial lung disease. Author(s): Fan LL, Kozinetz CA. Source: American Journal of Respiratory and Critical Care Medicine. 1997 September; 156(3 Pt 1): 939-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9310017&dopt=Abstract

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Familial dysautonomia: a diagnostic dilemma. chronic lung disease with signs of an autoimmune disease. Author(s): van Egmond-Frohlich AW, Paul K, Eggert W, Gaedicke G, Wahn U, Bauer CP. Source: Pediatric Pulmonology. 2001 June; 31(6): 478-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389582&dopt=Abstract

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Familial interstitial lung disease in children: response to chloroquine treatment in one sibling with desquamative interstitial pneumonitis. Author(s): Balasubramanyan N, Murphy A, O'Sullivan J, O'Connell EJ. Source: Pediatric Pulmonology. 1997 January; 23(1): 55-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9035199&dopt=Abstract

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Fatal obstructive lung disease after haploidentical sibling cord blood transplantation. Author(s): Ohnuma K, Toyoda Y, Ishida Y, Honda K, Nagao T, Ijiri R, Tanaka Y, Goto K, Hiroki K, Kigasawa H, Nishihira H. Source: Bone Marrow Transplantation. 1998 May; 21(9): 939-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613788&dopt=Abstract

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Fibroblast mitogenic activity of lung lavage fluid from infants with chronic lung disease of prematurity. Author(s): Currie AE, Kelly M, Vyas JR, Pandya H, Field D, Kotecha S. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 May; 86(3): F193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978752&dopt=Abstract

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Flock worker's lung: chronic interstitial lung disease in the nylon flocking industry. Author(s): Kern DG, Crausman RS, Durand KT, Nayer A, Kuhn C 3rd. Source: Annals of Internal Medicine. 1998 August 15; 129(4): 261-72. Erratum In: Ann Intern Med 1999 February 2; 130(3): 246. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9729178&dopt=Abstract

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Flow cytometry in the exploration of the physiopathology of occupational lung disease. Author(s): Curran AD. Source: Occupational and Environmental Medicine. 1999 November; 56(11): 742-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10658559&dopt=Abstract

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Fluorine-18-fluorodeoxyglucose uptake in rheumatoid arthritis-associated lung disease in a patient with thyroid cancer. Author(s): Bakheet SM, Powe J. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1998 February; 39(2): 234-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9476924&dopt=Abstract

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Follow up of a randomised trial of two different courses of dexamethasone for preterm babies at risk of chronic lung disease. Author(s): Armstrong DL, Penrice J, Bloomfield FH, Knight DB, Dezoete JA, Harding JE. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 March; 86(2): F102-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882552&dopt=Abstract

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Four-year incidence of allergic sensitization among schoolchildren in a community where allergy to cat and dog dominates sensitization: report from the Obstructive Lung Disease in Northern Sweden Study Group. Author(s): Ronmark E, Perzanowski M, Platts-Mills T, Lundback B; Obstructive Lung Disease in Northern Sweden Study Group. Source: The Journal of Allergy and Clinical Immunology. 2003 October; 112(4): 747-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564356&dopt=Abstract

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From clot to collagen: coagulation peptides in interstitial lung disease. Author(s): Dabbagh K, Chambers RC, Laurent GJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 May; 11(5): 1002-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9648946&dopt=Abstract

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Functional and antigenic concentrations of alpha-1-proteinase inhibitor after administration for the prevention of chronic lung disease of prematurity. Author(s): Stiskal JA, Ito S, Cox DW, Shennan AT, O'Brien KK, Kelly EN, Longley TB, Rabinovitch M, Dunn MS. Source: Biology of the Neonate. 1999 September; 76(3): 134-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10460951&dopt=Abstract

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Gains and losses from dexamethasone for neonatal chronic lung disease. Author(s): Greenough A. Source: Lancet. 1998 September 12; 352(9131): 835-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9742974&dopt=Abstract

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Gas exchange at rest during simulated altitude in patients with chronic lung disease. Author(s): Chi-Lem G, Perez-Padilla R. Source: Archives of Medical Research. 1998 Spring; 29(1): 57-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556924&dopt=Abstract

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Gastroesophageal reflux in very low birth weight infants: association with chronic lung disease and outcomes through 1 year of age. Author(s): Fuloria M, Hiatt D, Dillard RG, O'Shea TM. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2000 June; 20(4): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10879336&dopt=Abstract

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Gene therapy for lung disease. Author(s): Ennist DL. Source: Trends in Pharmacological Sciences. 1999 June; 20(6): 260-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10366870&dopt=Abstract

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Gene therapy for lung disease: hype or hope? Author(s): Albelda SM, Wiewrodt R, Zuckerman JB. Source: Annals of Internal Medicine. 2000 April 18; 132(8): 649-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766684&dopt=Abstract

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General management of chronic lung disease of premature infants. Author(s): Trittenwein G. Source: Pediatr Pulmonol Suppl. 1997; 16: 37-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443189&dopt=Abstract

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Genetic basis of familial interstitial lung disease: misfolding or function of surfactant protein C? Author(s): Whitsett JA. Source: American Journal of Respiratory and Critical Care Medicine. 2002 May 1; 165(9): 1201-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991863&dopt=Abstract

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Genetic influences and neonatal lung disease. Author(s): Hallman M, Haataja R. Source: Seminars in Neonatology : Sn. 2003 February; 8(1): 19-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667827&dopt=Abstract

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Genetics and pulmonary medicine. 1. The genetics of cystic fibrosis lung disease. Author(s): Davidson DJ, Porteous DJ. Source: Thorax. 1998 May; 53(5): 389-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9708232&dopt=Abstract

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Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Author(s): Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV. Source: Transplantation. 1998 October 27; 66(8): 1014-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9808485&dopt=Abstract

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Giant lamellar bodies in a case of Mycobacterium avium complex lung disease. Author(s): Sun AP, Ohtsuki Y, Fujita J, Shigeto E, Kohno N. Source: Pathology. 2002 October; 34(5): 473-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408350&dopt=Abstract

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Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease. Author(s): Gomez FP, Rodriguez-Roisin R. Source: Current Opinion in Pulmonary Medicine. 2002 March; 8(2): 81-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845001&dopt=Abstract

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Global initiative for chronic obstructive lung disease. Author(s): Gerald LB, Bailey WC. Source: Journal of Cardiopulmonary Rehabilitation. 2002 July-August; 22(4): 234-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202842&dopt=Abstract

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Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary. Author(s): Pauwels RA, Buist AS, Calverley PM, Jenkins CR, Hurd SS; GOLD Scientific Committee. Source: American Journal of Respiratory and Critical Care Medicine. 2001 April; 163(5): 1256-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316667&dopt=Abstract

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Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Author(s): Pauwels RA, Buist AS, Ma P, Jenkins CR, Hurd SS; GOLD Scientific Committee. Source: Respiratory Care. 2001 August; 46(8): 798-825. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463370&dopt=Abstract

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Global surveillance for antituberculosis-drug resistance, 1994-1997. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-Tuberculosis Drug Resistance Surveillance. Author(s): Pablos-Mendez A, Raviglione MC, Laszlo A, Binkin N, Rieder HL, Bustreo F, Cohn DL, Lambregts-van Weezenbeek CS, Kim SJ, Chaulet P, Nunn P. Source: The New England Journal of Medicine. 1998 June 4; 338(23): 1641-9. Erratum In: N England J Med 1998 July 9; 339(2): 139. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9614254&dopt=Abstract

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Global trends in resistance to antituberculosis drugs. World Health OrganizationInternational Union against Tuberculosis and Lung Disease Working Group on AntiTuberculosis Drug Resistance Surveillance. Author(s): Espinal MA, Laszlo A, Simonsen L, Boulahbal F, Kim SJ, Reniero A, Hoffner S, Rieder HL, Binkin N, Dye C, Williams R, Raviglione MC. Source: The New England Journal of Medicine. 2001 April 26; 344(17): 1294-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320389&dopt=Abstract

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Glucose metabolism in chronic lung disease. Author(s): Sauerwein HP, Schols AM. Source: Clinical Nutrition (Edinburgh, Lothian). 2002 October; 21(5): 367-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381332&dopt=Abstract

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Growth effects of systemic versus inhaled steroids in chronic lung disease. Author(s): Nicholl RM, Greenough A, King M, Cheeseman P, Gamsu HR. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 July; 87(1): F59-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091295&dopt=Abstract

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Growth in children with chronic lung disease. Author(s): Davis PB, Kercsmar CM. Source: The New England Journal of Medicine. 2000 March 23; 342(12): 887-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727595&dopt=Abstract

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Hard metal interstitial lung disease: high-resolution computed tomography appearance. Author(s): Gotway MB, Golden JA, Warnock M, Koth LL, Webb R, Reddy GP, Balmes JR. Source: Journal of Thoracic Imaging. 2002 October; 17(4): 314-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362071&dopt=Abstract

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Hard metal particles and lung disease: coincidence or causality? Author(s): Ruediger HW. Source: Respiration; International Review of Thoracic Diseases. 2000; 67(2): 137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10858124&dopt=Abstract

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Health care utilisation of infants with chronic lung disease, related to hospitalisation for RSV infection. Author(s): Greenough A, Cox S, Alexander J, Lenney W, Turnbull F, Burgess S, Chetcuti PA, Shaw NJ, Woods A, Boorman J, Coles S, Turner J. Source: Archives of Disease in Childhood. 2001 December; 85(6): 463-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719328&dopt=Abstract

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Hematologic alterations and CO(2) hypersensitivity in male panic disorder patients and normal controls: similarities to high-altitude hypoxia and chronic lung disease. Author(s): Ross DC, Preter M, Klein DF. Source: Depression and Anxiety. 2001; 14(2): 153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668670&dopt=Abstract

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Hepatoblastoma in a low-birthweight infant complicated with cleft palate, DandyWalker malformation and chronic lung disease. Author(s): Kisato Y, Nishikubo T, Uchida Y, Kuwahara I, Minowa H, Kamitsuji H, Kanehiro H, Park YD, Sasaki F. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 December; 44(6): 698-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421276&dopt=Abstract

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High thoracic epidural anesthesia for coronary artery bypass graft surgery in a patient with severe obstructive lung disease. Author(s): Visser WA, Liem TH, Brouwer RM. Source: Journal of Cardiothoracic and Vascular Anesthesia. 2001 December; 15(6): 75860. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748529&dopt=Abstract

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High-frequency oscillation and chronic lung disease in very low birth weight infants. Author(s): Thome U, Pohlandt F. Source: Pediatrics. 2001 July; 108(1): 213-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11686122&dopt=Abstract

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High-frequency oscillation and chronic lung disease in very low birth weight infants. Author(s): Shenai JP. Source: Pediatrics. 2001 July; 108(1): 212-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11452961&dopt=Abstract

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High-frequency oscillatory ventilation for the prevention of chronic lung disease of prematurity. Author(s): Johnson AH, Peacock JL, Greenough A, Marlow N, Limb ES, Marston L, Calvert SA; United Kingdom Oscillation Study Group. Source: The New England Journal of Medicine. 2002 August 29; 347(9): 633-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200550&dopt=Abstract

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High-resolution CT of diffuse interstitial lung disease: key findings in common disorders. Author(s): Schaefer-Prokop C, Prokop M, Fleischmann D, Herold C. Source: European Radiology. 2001; 11(3): 373-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11288840&dopt=Abstract

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High-resolution CT of diffuse lung disease: value and limitations. Author(s): Hansell DM. Source: Radiologic Clinics of North America. 2001 November; 39(6): 1091-113. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11699663&dopt=Abstract

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High-resolution CT of drug-induced lung disease. Author(s): Erasmus JJ, McAdams HP, Rossi SE. Source: Radiologic Clinics of North America. 2002 January; 40(1): 61-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813820&dopt=Abstract

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High-resolution CT of lung disease related to collagen vascular disease. Author(s): Franquet T. Source: Radiologic Clinics of North America. 2001 November; 39(6): 1171-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11699667&dopt=Abstract

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High-resolution CT of paediatric lung disease. Author(s): Copley SJ, Padley SP. Source: European Radiology. 2001; 11(12): 2564-75. Epub 2001 August 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11734960&dopt=Abstract

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High-resolution CT of pediatric lung disease. Author(s): Kuhn JP, Brody AS. Source: Radiologic Clinics of North America. 2002 January; 40(1): 89-110. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813822&dopt=Abstract

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hnRNP B1 expression in benign and malignant lung disease. Author(s): Snead DR, Perunovic B, Cullen N, Needham M, Dhillon DP, Satoh H, Kamma H. Source: The Journal of Pathology. 2003 May; 200(1): 88-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692846&dopt=Abstract

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Home oxygen status and rehospitalisation and primary care requirements of infants with chronic lung disease. Author(s): Greenough A, Alexander J, Burgess S, Chetcuti PA, Cox S, Lenney W, Turnbull F, Shaw NJ, Woods A, Boorman J, Coles S, Turner J. Source: Archives of Disease in Childhood. 2002 January; 86(1): 40-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806882&dopt=Abstract

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Hospice care for patients with advanced lung disease. Author(s): Abrahm JL, Hansen-Flaschen J. Source: Chest. 2002 January; 121(1): 220-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11796455&dopt=Abstract

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Hydatid lung disease (echinococcosis/hydatidosis). Author(s): Gottstein B, Reichen J. Source: Clinics in Chest Medicine. 2002 June; 23(2): 397-408, Ix. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092034&dopt=Abstract

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Hyperacidification in cystic fibrosis: links with lung disease and new prospects for treatment. Author(s): Poschet J, Perkett E, Deretic V. Source: Trends in Molecular Medicine. 2002 November; 8(11): 512-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421684&dopt=Abstract

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Imaging in lung disease. Author(s): Decramer M, Roussos C. Source: Eur Respir J Suppl. 2002 February; 35: 1S-2S. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064676&dopt=Abstract

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Imaging of nonmalignant occupational lung disease. Author(s): Kim JS, Lynch DA. Source: Journal of Thoracic Imaging. 2002 October; 17(4): 238-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362064&dopt=Abstract

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Imipenem in acute lung infections and bacterial re-exacerbations of chronic obstructive lung disease. Author(s): Pozzi E, De Rose V. Source: Journal of Chemotherapy (Florence, Italy). 1991 January; 3 Suppl 1: 213-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041768&dopt=Abstract

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Immunoglobulin-E and anti-IgE treatment in lung disease. Author(s): Chitkara RK, Sarinas PS, Fick RB Jr. Source: Monaldi Arch Chest Dis. 2001 December; 56(6): 514-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980283&dopt=Abstract

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Impact of interstitial lung disease on surgical morbidity and mortality for lung cancer: analyses of short-term and long-term outcomes. Author(s): Chiyo M, Sekine Y, Iwata T, Tatsumi K, Yasufuku K, Iyoda A, Otsuji M, Yoshida S, Shibuya K, Iizasa T, Saitoh Y, Fujisawa T. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 October; 126(4): 11416. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14566260&dopt=Abstract

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Implications for matrix metalloproteinases as modulators of pediatric lung disease. Author(s): Winkler MK, Foldes JK, Bunn RC, Fowlkes JL. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 April; 284(4): L557-65. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456387&dopt=Abstract

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Improving nutritional support in chronic lung disease. Author(s): Hankard R. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 April; 36(4): 432-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658030&dopt=Abstract

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In vivo penicillin MIC drift to extremely high resistance in Serotype 14 Streptococcus pneumoniae persistently colonizing the nasopharynx of an infant with chronic suppurative lung disease: a case study. Author(s): Leach AJ, Morris PS, Smith-Vaughan H, Mathews JD. Source: Antimicrobial Agents and Chemotherapy. 2002 November; 46(11): 3648-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384383&dopt=Abstract

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Increased epithelial cell proliferation in very premature baboons with chronic lung disease. Author(s): Maniscalco WM, Watkins RH, O'Reilly MA, Shea CP. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2002 November; 283(5): L991-L1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376352&dopt=Abstract

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Increased vitronectin and endothelin-1 in the breath condensate of patients with fibrosing lung disease. Author(s): Carpagnano GE, Kharitonov SA, Wells AU, Pantelidis P, Du Bois RM, Barnes PJ. Source: Respiration; International Review of Thoracic Diseases. 2003 March-April; 70(2): 154-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740512&dopt=Abstract

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Influence of underlying lung disease on early postoperative course after single lung transplantation. Author(s): Ceriana P, Klersy C, Veronesi R, Braschi A, D'Armini A, Vigano M. Source: The Journal of Cardiovascular Surgery. 2002 October; 43(5): 715-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386591&dopt=Abstract

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Inhaled P2Y2 receptor agonists as a treatment for patients with Cystic Fibrosis lung disease. Author(s): Kellerman D, Evans R, Mathews D, Shaffer C. Source: Advanced Drug Delivery Reviews. 2002 December 5; 54(11): 1463-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458155&dopt=Abstract

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Inhaled versus systemic corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates. Author(s): Shah SS, Ohlsson A, Halliday H, Shah VS. Source: Cochrane Database Syst Rev. 2003; (1): Cd002058. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535425&dopt=Abstract

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Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants. Author(s): Shah SS, Ohlsson A, Halliday H, Shah VS. Source: Cochrane Database Syst Rev. 2003; (2): Cd002057. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804423&dopt=Abstract

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Interstitial lung disease associated with juvenile dermatomyositis: clinical features and efficacy of cyclosporin A. Author(s): Kobayashi I, Yamada M, Takahashi Y, Kawamura N, Okano M, Sakiyama Y, Kobayashi K. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 371-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595639&dopt=Abstract

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Interstitial lung disease in an intravenous drug user. Author(s): Conen D, Schilter D, Bubendorf L, Brutsche MH, Leuppi JD. Source: Respiration; International Review of Thoracic Diseases. 2003 January-February; 70(1): 101-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584400&dopt=Abstract

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Interstitial lung disease in polymyositis and dermatomyositis. Author(s): Marie I, Hachulla E, Cherin P, Dominique S, Hatron PY, Hellot MF, Devulder B, Herson S, Levesque H, Courtois H. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 614-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522835&dopt=Abstract

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Interstitial lung disease in polymyositis and dermatomyositis: clinical course and response to treatment. Author(s): Schnabel A, Reuter M, Biederer J, Richter C, Gross WL. Source: Seminars in Arthritis and Rheumatism. 2003 April; 32(5): 273-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701038&dopt=Abstract

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Interstitial lung disease in scleroderma. Author(s): White B. Source: Rheumatic Diseases Clinics of North America. 2003 May; 29(2): 371-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841300&dopt=Abstract

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Interstitial lung disease in systemic sclerosis. Author(s): Ooi GC, Mok MY, Tsang KW, Wong Y, Khong PL, Fung PC, Chan S, Tse HF, Wong RW, Lam WK, Lau CS. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2003 May; 44(3): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751995&dopt=Abstract

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KL-6 is a potential marker for interstitial lung disease associated with juvenile dermatomyositis. Author(s): Kobayashi I, Ono S, Kawamura N, Okano M, Miyazawa K, Shibuya H, Kobayashi K. Source: The Journal of Pediatrics. 2001 February; 138(2): 274-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174630&dopt=Abstract

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KL-6, a mucinous glycoprotein, as an indicator of chronic lung disease of the newborn. Author(s): Ogihara T, Hirano K, Morinobu T, Ogawa S, Hiroi M, Ban R, Ogihara H, Tamai H. Source: The Journal of Pediatrics. 2000 August; 137(2): 280-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10931429&dopt=Abstract

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Laboratory assessment of fitness to fly in patients with lung disease: a practical approach. Author(s): Robson AG, Hartung TK, Innes JA. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 August; 16(2): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968494&dopt=Abstract

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Length of gestation period linked to chronic lung disease. Author(s): Pound A. Source: Lancet. 2001 November 3; 358(9292): 1518. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705572&dopt=Abstract

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Leucine kinetics during simultaneously administered insulin and dexamethasone in preterm infants with severe lung disease. Author(s): van Beek RH, Zimmermann LJ, Vergunst van Keulen JG, Carnielli VP, Wattimena DJ, van Goudoever JB, Sauer PJ. Source: Pediatric Research. 2001 March; 49(3): 373-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228263&dopt=Abstract

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Leukemoid reaction and chronic lung disease in infants with very low birth weight. Author(s): Nakamura T, Ezaki S, Takasaki J, Itabashi K, Ogawa Y. Source: J Matern Fetal Neonatal Med. 2002 June;11(6):396-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12389655&dopt=Abstract

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Levitating consolidation in eosinophilic lung disease. Author(s): Sheehan RE, English J, Wittmann R, Muller NL. Source: Journal of Thoracic Imaging. 2003 January; 18(1): 45-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544747&dopt=Abstract

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Listing for lung transplantation: life expectancy and transplant effect, stratified by type of end-stage lung disease, the Eurotransplant experience. Author(s): De Meester J, Smits JM, Persijn GG, Haverich A. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2001 May; 20(5): 518-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11343978&dopt=Abstract

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Liver transplantation for massive hepatic haemangiomatosis causing restrictive lung disease. Author(s): Keegan MT, Kamath GS, Vasdev GM, Findlay JY, Gores GJ, Steers JL, Plevak DJ. Source: British Journal of Anaesthesia. 2001 March; 86(3): 431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573537&dopt=Abstract

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Long term results of lung resection in cystic fibrosis patients with localised lung disease. Author(s): Lucas JS, Connett GJ, Fairhurst J. Source: Archives of Disease in Childhood. 2002 January; 86(1): 66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806895&dopt=Abstract

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Long term sequelae of bronchopulmonary dysplasia (chronic lung disease of infancy). Author(s): Eber E, Zach MS. Source: Thorax. 2001 April; 56(4): 317-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254826&dopt=Abstract

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Lower concentration of pulmonary hepatocyte growth factor is associated with more severe lung disease in preterm infants. Author(s): Lassus P, Heikkila P, Andersson LC, von Boguslawski K, Andersson S. Source: The Journal of Pediatrics. 2003 August; 143(2): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970632&dopt=Abstract

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Lung biopsy in diffuse parenchymal lung disease. Author(s): Glaspole IN, Wells AU, du Bois RM. Source: Monaldi Arch Chest Dis. 2001 June; 56(3): 225-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11665502&dopt=Abstract

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Lung disease associated with the IVS8 5T allele of the CFTR gene. Author(s): Noone PG, Pue CA, Zhou Z, Friedman KJ, Wakeling EL, Ganeshananthan M, Simon RH, Silverman LM, Knowles MR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 November; 162(5): 1919-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069835&dopt=Abstract

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Lung disease in cystic fibrosis: is airway surface liquid composition abnormal? Author(s): Verkman AS. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2001 August; 281(2): L306-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11435202&dopt=Abstract

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Lung disease. Author(s): Tan RA, Spector SL. Source: Clin Allergy Immunol. 2000; 15: 175-97. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943293&dopt=Abstract

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Lung epithelial ion transport in neonatal lung disease. Author(s): Pitkanen O. Source: Biology of the Neonate. 2001 May; 80 Suppl 1: 14-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359039&dopt=Abstract

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Lung function measured by the oscillometric method in prematurely born children with chronic lung disease. Author(s): Malmberg LP, Mieskonen S, Pelkonen A, Kari A, Sovijarvi AR, Turpeinen M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 October; 16(4): 598-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11106198&dopt=Abstract

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Lung function testing: chronic lung disease of infancy. Author(s): Allen JL, Panitch HB. Source: Pediatric Pulmonology. 2001; Suppl 23: 138-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886119&dopt=Abstract

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Lung recruitment in unilateral lung disease. Author(s): Blanch L, Murias G, Nahum A. Source: Minerva Anestesiol. 2002 May; 68(5): 351-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029244&dopt=Abstract

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Lung transplantation in interstitial lung disease. Author(s): Sulica R, Teirstein A, Padilla ML. Source: Current Opinion in Pulmonary Medicine. 2001 September; 7(5): 314-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584182&dopt=Abstract

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Lungs of gold: the global initiative for chronic obstructive lung disease (GOLD). Author(s): Rees J. Source: Int J Clin Pract. 2001 September; 55(7): 429-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594248&dopt=Abstract

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Maintenance after pulmonary rehabilitation in chronic lung disease: a randomized trial. Author(s): Ries AL, Kaplan RM, Myers R, Prewitt LM. Source: American Journal of Respiratory and Critical Care Medicine. 2003 March 15; 167(6): 880-8. Epub 2002 December 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505859&dopt=Abstract

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Management of dyspnea in patients with far-advanced lung disease. Author(s): Markowitz AJ, Rabow M. Source: Jama : the Journal of the American Medical Association. 2002 May 1; 287(17): 2261. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980526&dopt=Abstract

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Measuring quality of life in interstitial lung disease. Author(s): De Vries J, Drent M. Source: Chest. 2000 July; 118(1): 275. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893399&dopt=Abstract

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Medicine: Smoke signals for lung disease. Author(s): Roberts AB. Source: Nature. 2003 March 13; 422(6928): 130-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634771&dopt=Abstract

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MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients. Author(s): Viglio S, Iadarola P, Lupi A, Trisolini R, Tinelli C, Balbi B, Grassi V, Worlitzsch D, Doring G, Meloni F, Meyer KC, Dowson L, Hill SL, Stockley RA, Luisetti M. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 June; 15(6): 1039-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885422&dopt=Abstract

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Microbial infection and inflammation in the development of chronic lung disease of prematurity. Author(s): Li YH, Tullus K. Source: Microbes and Infection / Institut Pasteur. 2002 June; 4(7): 723-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067832&dopt=Abstract

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Miliary lung disease revisited. Author(s): Andreu J, Mauleon S, Pallisa E, Majo J, Martinez-Rodriguez M, Caceres J. Source: Current Problems in Diagnostic Radiology. 2002 September-October; 31(5): 18997. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419999&dopt=Abstract

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Moderately early (7-14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants. Author(s): Halliday HL, Ehrenkranz RA, Doyle LW. Source: Cochrane Database Syst Rev. 2003; (1): Cd001144. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535400&dopt=Abstract

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Modifier genes in cystic fibrosis lung disease. Author(s): Merlo CA, Boyle MP. Source: The Journal of Laboratory and Clinical Medicine. 2003 April; 141(4): 237-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677168&dopt=Abstract

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Moment ratio analysis of multiple breath nitrogen washout in infants with lung disease. Author(s): Schibler A, Schneider M, Frey U, Kraemer R. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2000 June; 15(6): 1094-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885429&dopt=Abstract

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Monitoring cardiovascular function in infants with chronic lung disease of prematurity. Author(s): Abman SH. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 July; 87(1): F15-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091282&dopt=Abstract

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Multidetector-row CT and interstitial lung disease. Author(s): Hunsaker AR. Source: Semin Roentgenol. 2003 April; 38(2): 176-85. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854441&dopt=Abstract

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Multiple courses of antenatal corticosteroids are associated with early severe lung disease in preterm neonates. Author(s): Banks BA, Macones G, Cnaan A, Merrill JD, Ballard PL, Ballard RA; North American TRH Study Group. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2002 March; 22(2): 101-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896513&dopt=Abstract

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Mycobacterium avium complex lung disease in immunocompetent patients: radiography-CT correlation. Author(s): Wittram C, Weisbrod GL. Source: The British Journal of Radiology. 2002 April; 75(892): 340-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000692&dopt=Abstract

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Mycobacterium avium complex pulmonary disease in patients with pre-existing lung disease. Author(s): Aksamit TR. Source: Clinics in Chest Medicine. 2002 September; 23(3): 643-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371000&dopt=Abstract

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Nebulised morphine for severe interstitial lung disease. Author(s): Polosa R, Simidchiev A, Walters EH. Source: Cochrane Database Syst Rev. 2002; (3): Cd002872. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137662&dopt=Abstract

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Neonatal chronic lung disease. Author(s): Falcao MC. Source: Revista Do Hospital Das Clinicas. 1999 November-December; 54(6): 173-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881063&dopt=Abstract

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Neonatal lung disease. Author(s): Kirpalani H. Source: Paediatric Respiratory Reviews. 2003 March; 4(1): 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615025&dopt=Abstract

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New therapeutic approaches for cystic fibrosis lung disease. Author(s): Davies JC. Source: Journal of the Royal Society of Medicine. 2002; 95 Suppl 41: 58-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12216276&dopt=Abstract

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Newly diagnosed chronic obstructive pulmonary disease. Clinical features and distribution of the novel stages of the Global Initiative for Obstructive Lung Disease. Author(s): Kornmann O, Beeh KM, Beier J, Geis UP, Ksoll M, Buhl R; Global Initiative for Obstructive Lung Disease. Source: Respiration; International Review of Thoracic Diseases. 2003 January-February; 70(1): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584394&dopt=Abstract

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Non-compliance in adolescents with chronic lung disease: causative factors and practical approach. Author(s): Fitzgerald D. Source: Paediatric Respiratory Reviews. 2001 September; 2(3): 260-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052328&dopt=Abstract

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Noninvasive nocturnal ventilatory support in advanced lung disease from cystic fibrosis. Author(s): Granton JT, Shapiro C, Kesten S. Source: Respiratory Care. 2002 June; 47(6): 675-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036437&dopt=Abstract

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Nontuberculous mycobacteria. II: nested-cohort study of impact on cystic fibrosis lung disease. Author(s): Olivier KN, Weber DJ, Lee JH, Handler A, Tudor G, Molina PL, Tomashefski J, Knowles MR; Nontuberculous Mycobacteria in Cystic Fibrosis Study Group. Source: American Journal of Respiratory and Critical Care Medicine. 2003 March 15; 167(6): 835-40. Epub 2002 November 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433669&dopt=Abstract

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Non-viral approach toward gene therapy of cystic fibrosis lung disease. Author(s): Bragonzi A, Conese M. Source: Current Gene Therapy. 2002 September; 2(3): 295-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189717&dopt=Abstract

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Not 15 but 50% of smokers develop COPD?--Report from the Obstructive Lung Disease in Northern Sweden Studies. Author(s): Lundback B, Lindberg A, Lindstrom M, Ronmark E, Jonsson AC, Jonsson E, Larsson LG, Andersson S, Sandstrom T, Larsson K; Obstructive Lung Disease in Northern Sweden Studies. Source: Respiratory Medicine. 2003 February; 97(2): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587960&dopt=Abstract

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Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Author(s): Mannino DM, Ford ES, Redd SC. Source: The American Journal of Medicine. 2003 June 15; 114(9): 758-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829203&dopt=Abstract

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Obstructive lung disease and low lung function in adults in the United States: data from the National Health and Nutrition Examination Survey, 1988-1994. Author(s): Mannino DM, Gagnon RC, Petty TL, Lydick E. Source: Archives of Internal Medicine. 2000 June 12; 160(11): 1683-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10847262&dopt=Abstract

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Occupational lung disease related to cytophaga endotoxin exposure in a nylon plant. Author(s): Nordness ME, Zacharisen MC, Schlueter DP, Fink JN. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 2003 April; 45(4): 385-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708142&dopt=Abstract

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Occupational lung disease. Part 1. Identifying work-related asthma and other disorders. Author(s): Kuschner WG, Stark P. Source: Postgraduate Medicine. 2003 April; 113(4): 70-2, 75-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718236&dopt=Abstract

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Occupational lung disease. Part 2. Discovering the cause of diffuse parenchymal lung disease. Author(s): Kuschner WG, Stark P. Source: Postgraduate Medicine. 2003 April; 113(4): 81-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718237&dopt=Abstract

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Occurrence of farmer's lung disease is relevant to meteorological conditions: a 20-year follow-up field survey analysis. Author(s): Takahashi T, Ohtsuka Y, Munakata M, Nasuhara Y, Kamachi-Satoh A, Homma Y, Kawakami Y. Source: American Journal of Industrial Medicine. 2002 June; 41(6): 506-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12173376&dopt=Abstract

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Open lung biopsy in diffuse infiltrative lung disease with progressive dyspnoea: is it useful? Author(s): Arora VK, Gupta R, Johri A. Source: Indian J Chest Dis Allied Sci. 2002 July-September; 44(3): 203-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206483&dopt=Abstract

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Organic antigen-induced interstitial lung disease: diagnosis and management. Author(s): Jacobs RL, Andrews CP, Coalson J. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 January; 88(1): 30-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11814275&dopt=Abstract

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Oxidant stress stimulates anion secretion from the human airway epithelial cell line Calu-3: implications for cystic fibrosis lung disease. Author(s): Cowley EA, Linsdell P. Source: The Journal of Physiology. 2002 August 15; 543(Pt 1): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181292&dopt=Abstract

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Oxygen therapy for infants with chronic lung disease. Author(s): Kotecha S, Allen J. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 July; 87(1): F11-4. Review. Erratum In: Arch Dis Child Fetal Neonatal Ed 2002 November; 87(3): F234. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091281&dopt=Abstract

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Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung disease. Author(s): Girgis RE, Gugnani MK, Abrams J, Mayes MD. Source: American Journal of Respiratory and Critical Care Medicine. 2002 June 15; 165(12): 1587-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070057&dopt=Abstract

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Patterns of colonization with Ureaplasma urealyticum during neonatal intensive care unit hospitalizations of very low birth weight infants and the development of chronic lung disease. Author(s): Castro-Alcaraz S, Greenberg EM, Bateman DA, Regan JA. Source: Pediatrics. 2002 October; 110(4): E45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359818&dopt=Abstract

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Pediatric interstitial lung disease: children are not small adults. Author(s): Fan LL, Langston C. Source: American Journal of Respiratory and Critical Care Medicine. 2002 June 1; 165(11): 1466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045116&dopt=Abstract

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Placental and other perinatal risk factors for chronic lung disease in very low birth weight infants. Author(s): Redline RW, Wilson-Costello D, Hack M. Source: Pediatric Research. 2002 November; 52(5): 713-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409518&dopt=Abstract

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Platelet endothelial cell adhesion molecule-1 and capillary loading in premature infants with and without chronic lung disease. Author(s): Olsen SL, Thibeault DW, Mabry SM, Norberg M, Truog WE. Source: Pediatric Pulmonology. 2002 April; 33(4): 255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921454&dopt=Abstract

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Postnatal glucocorticosteroids for chronic lung disease in preterm neonates: a definite no. Author(s): Patole S, Vijayakumar P. Source: Indian Pediatrics. 2002 September; 39(9): 888; Author Reply 889-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368549&dopt=Abstract

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Potential role of macrolide antibiotics in the management of cystic fibrosis lung disease. Author(s): Nguyen T, Louie SG, Beringer PM, Gill MA. Source: Current Opinion in Pulmonary Medicine. 2002 November; 8(6): 521-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394161&dopt=Abstract

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Pulmonary function and exercise capacity for ELBW survivors in preadolescence: effect of neonatal chronic lung disease. Author(s): Kilbride HW, Gelatt MC, Sabath RJ. Source: The Journal of Pediatrics. 2003 October; 143(4): 488-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14571227&dopt=Abstract

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Pulmonary interstitial glycogenosis: a new variant of neonatal interstitial lung disease. Author(s): Canakis AM, Cutz E, Manson D, O'Brodovich H. Source: American Journal of Respiratory and Critical Care Medicine. 2002 June 1; 165(11): 1557-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045133&dopt=Abstract

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Pulmonary vein stenosis mimicking chronic lung disease. Author(s): Chakrabarti S, Tsao S, Vettukattil JJ, Gnanapragasam JP. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 July; 92(7): 857-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892169&dopt=Abstract

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Qualitative aspects of exertional dyspnea in patients with interstitial lung disease. Author(s): O'Donnell DE, Chau LK, Webb KA. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1998 June; 84(6): 2000-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9609795&dopt=Abstract

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Qualitative assessment of general movements in high-risk preterm infants with chronic lung disease requiring dexamethasone therapy. Author(s): Bos AF, Martijn A, van Asperen RM, Hadders-Algra M, Okken A, Prechtl HF. Source: The Journal of Pediatrics. 1998 February; 132(2): 300-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9506645&dopt=Abstract

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Radiology of acute diffuse lung disease in the immunocompetent host. Author(s): Ketai L, Washington L. Source: Semin Roentgenol. 2002 January; 37(1): 25-36. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987763&dopt=Abstract

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Randomised double blind placebo controlled trial of inhaled fluticasone propionate in infants with chronic lung disease. Author(s): Beresford MW, Primhak R, Subhedar NV, Shaw NJ. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 July; 87(1): F62-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091296&dopt=Abstract

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Rapidly progressive interstitial lung disease in a dermatomyositis patient with high levels of creatine phosphokinase, severe muscle symptoms and positive anti-Jo-1 antibody. Author(s): Kashiwabara K, Ota K. Source: Intern Med. 2002 July; 41(7): 584-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132530&dopt=Abstract

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Repeat positive cultures in Mycobacterium intracellulare lung disease after macrolide therapy represent new infections in patients with nodular bronchiectasis. Author(s): Wallace Jr RJ, Zhang Y, Brown-Elliott BA, Yakrus MA, Wilson RW, Mann L, Couch L, Girard WM, Griffith DE. Source: The Journal of Infectious Diseases. 2002 July 15; 186(2): 266-73. Epub 2002 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134265&dopt=Abstract

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Review: occupational and environmental lung disease. Author(s): Singh N, Davis GS. Source: Current Opinion in Pulmonary Medicine. 2002 March; 8(2): 117-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845007&dopt=Abstract

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Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease. Author(s): Verkman AS, Song Y, Thiagarajah JR. Source: American Journal of Physiology. Cell Physiology. 2003 January; 284(1): C2-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475759&dopt=Abstract

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Role of defensins in inflammatory lung disease. Author(s): Aarbiou J, Rabe KF, Hiemstra PS. Source: Annals of Medicine. 2002; 34(2): 96-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108580&dopt=Abstract

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Role of oxidant injury in the pathogenesis of neonatal lung disease. Author(s): Davis JM. Source: Acta Paediatrica (Oslo, Norway : 1992). Supplement. 2002; 91(437): 23-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200893&dopt=Abstract

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Roles for insulin-like growth factor I and transforming growth factor-beta in fibrotic lung disease. Author(s): Krein PM, Winston BW. Source: Chest. 2002 December; 122(6 Suppl): 289S-293S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475802&dopt=Abstract

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Roles of bioavailable iron and calcium in coal dust-induced oxidative stress: possible implications in coal workers' lung disease. Author(s): Zhang Q, Dai J, Ali A, Chen L, Huang X. Source: Free Radical Research. 2002 March; 36(3): 285-94. Erratum In: Free Radic Res 2002 August; 36(8): 929. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071347&dopt=Abstract

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Safety of palivizumab in preterm infants 29 to 32 weeks' gestational age without chronic lung disease to prevent serious respiratory syncytial virus infection. Author(s): Groothuis JR. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 July; 22(7): 414-7. Epub 2003 June 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827537&dopt=Abstract

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Scintigraphic diagnosis of a right to left shunt in end-stage lung disease. Author(s): Graves MW, Kiratli PO, Mozley D, Palevsky H, Zukerberg B, Alavi A. Source: Respiratory Medicine. 2003 May; 97(5): 549-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735674&dopt=Abstract

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Serum neutrophil elastase levels predict initial clinical condition but do not correlate with the progression of interstitial lung disease. Author(s): Lopez-Campos Bodineau JL, Rodriguez Becerra E, Cayuela Dominguez A, Laserna Martinez E, Fernandez Vega D, Rodriguez Matute C, Castillo Gomez J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 January; 9(1): Cr1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552241&dopt=Abstract

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Sleep quality and daytime function in adults with cystic fibrosis and severe lung disease. Author(s): Dancey DR, Tullis ED, Heslegrave R, Thornley K, Hanly PJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 March; 19(3): 504-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936530&dopt=Abstract

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Small airway involvement in interstitial lung disease: radiologic evidence. Author(s): Wilcox AG. Source: Current Opinion in Pulmonary Medicine. 2000 September; 6(5): 399-403. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10958229&dopt=Abstract

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Statement on the care of the child with chronic lung disease of infancy and childhood. Author(s): Allen J, Zwerdling R, Ehrenkranz R, Gaultier C, Geggel R, Greenough A, Kleinman R, Klijanowicz A, Martinez F, Ozdemir A, Panitch HB, Nickerson B, Stein MT, Tomezsko J, Van Der Anker J; American Thoracic Society. Source: American Journal of Respiratory and Critical Care Medicine. 2003 August 1; 168(3): 356-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888611&dopt=Abstract

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Successful treatment of progressive rheumatoid interstitial lung disease with cyclosporine: a case report. Author(s): Chang HK, Park W, Ryu DS. Source: Journal of Korean Medical Science. 2002 April; 17(2): 270-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961317&dopt=Abstract

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Surgical resection of lung cancer in patients with underlying interstitial lung disease. Author(s): Martinod E, Azorin JF, Sadoun D, Destable MD, Le Toumelin P, Longchampt E, Kambouchner M, Guillevin L, Valeyre D. Source: The Annals of Thoracic Surgery. 2002 October; 74(4): 1004-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400736&dopt=Abstract

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Survey of patients' views of domiciliary nebuliser treatment for chronic lung disease. Author(s): Barta SK, Crawford A, Roberts CM. Source: Respiratory Medicine. 2002 June; 96(6): 375-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117035&dopt=Abstract

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Systemic sclerosis and interstitial lung disease: a pilot study using pulse intravenous methylprednisolone and cyclophosphamide to assess the effect on high resolution computed tomography scan and lung function. Author(s): Griffiths B, Miles S, Moss H, Robertson R, Veale D, Emery P. Source: The Journal of Rheumatology. 2002 November; 29(11): 2371-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415594&dopt=Abstract

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The aurora sign: an ultrasonographic sign suggesting parenchymal lung disease. Author(s): Kohzaki S, Tsurusaki K, Uetani M, Nakanishi K, Hayashi K. Source: The British Journal of Radiology. 2003 July; 76(907): 437-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857701&dopt=Abstract

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The changing landscape of HIV-related lung disease in the era of highly active antiretroviral therapy. Author(s): O'Neil KM. Source: Chest. 2002 September; 122(3): 768-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226010&dopt=Abstract

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The proportional Venn diagram of obstructive lung disease: two approximations from the United States and the United Kingdom. Author(s): Soriano JB, Davis KJ, Coleman B, Visick G, Mannino D, Pride NB. Source: Chest. 2003 August; 124(2): 474-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907531&dopt=Abstract

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The structural basis of pulmonary hypertension in chronic lung disease: remodelling, rarefaction or angiogenesis? Author(s): Hopkins N, McLoughlin P. Source: Journal of Anatomy. 2002 October; 201(4): 335-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430958&dopt=Abstract

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Thrice-weekly clarithromycin-containing regimen for treatment of Mycobacterium kansasii lung disease: results of a preliminary study. Author(s): Griffith DE, Brown-Elliott BA, Wallace RJ Jr. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 November 1; 37(9): 1178-82. Epub 2003 October 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557961&dopt=Abstract

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Total pulmonary vein occlusion as a consequence of catheter ablation for atrial fibrillation mimicking primary lung disease. Author(s): Ernst S, Ouyang F, Goya M, Lober F, Schneider C, Hoffmann-Riem M, Schwarz S, Hornig K, Muller KM, Antz M, Kaukel E, Kugler C, Kuck KH. Source: Journal of Cardiovascular Electrophysiology. 2003 April; 14(4): 366-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741706&dopt=Abstract

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Treating preterm infants at risk for chronic lung disease with dexamethasone leads to an impaired quality of general movements. Author(s): Bos AF, Dibiasi J, Tiessen AH, Bergman KA. Source: Biology of the Neonate. 2002; 82(3): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373065&dopt=Abstract

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Treatment of Mycobacterium avium-intracellulare complex lung disease with a macrolide, ethambutol, and clofazimine. Author(s): Field SK, Cowie RL. Source: Chest. 2003 October; 124(4): 1482-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14555583&dopt=Abstract

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Troponin T elevation in lobar lung disease. Author(s): Weinberg I, Cukierman T, Chajek-Shaul T. Source: Postgraduate Medical Journal. 2002 April; 78(918): 244-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930030&dopt=Abstract

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Tuberculosis in children dying with HIV-related lung disease: clinical-pathological correlations. Author(s): Rennert WP, Kilner D, Hale M, Stevens G, Stevens W, Crewe-Brown H. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2002 September; 6(9): 806-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234136&dopt=Abstract

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Understanding the mechanisms of infant respiratory distress and chronic lung disease. Author(s): Copland IB, Post M. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 March; 26(3): 261-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867331&dopt=Abstract

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Unusual systemic disorders associated with interstitial lung disease. Author(s): Sharma OP. Source: Current Opinion in Pulmonary Medicine. 2001 September; 7(5): 291-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11584178&dopt=Abstract

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Update on lung disease in AIDS. Author(s): Boiselle PM, Aviram G, Fishman JE. Source: Semin Roentgenol. 2002 January; 37(1): 54-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987767&dopt=Abstract

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Urinary beta 2-microglobulin in premature infants with chorioamnionitis and chronic lung disease. Author(s): Nishimaki S, Shima Y, Sato M, An H, Hashimoto M, Nishiyama Y, Iwasaki S, Tateishi I, Seki K, Yokota S. Source: The Journal of Pediatrics. 2003 July; 143(1): 120-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915837&dopt=Abstract

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Urinary tract infection with Trichomonas vaginalis in a premature newborn infant and the development of chronic lung disease. Author(s): Hoffman DJ, Brown GD, Wirth FH, Gebert BS, Bailey CL, Anday EK. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2003 January; 23(1): 59-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556929&dopt=Abstract

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Use of an artificial neural network to determine the diagnostic value of specific clinical and radiologic parameters in the diagnosis of interstitial lung disease on chest radiographs. Author(s): Abe H, Ashizawa K, Katsuragawa S, MacMahon H, Doi K. Source: Academic Radiology. 2002 January; 9(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918354&dopt=Abstract

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Use of forced inspiratory vital capacity to identify bronchodilator reversibility in obstructive lung disease. Author(s): Biring MS, Madison S, Mohsenifar Z. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 2001 September; 38(6): 495-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642416&dopt=Abstract

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Usefulness of coronal reformations in the diagnostic evaluation of infiltrative lung disease. Author(s): Remy-Jardin M, Campistron P, Amara A, Mastora I, Tillie-Leblond I, Delannoy V, Duhamel A, Remy J. Source: Journal of Computer Assisted Tomography. 2003 March-April; 27(2): 266-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703024&dopt=Abstract

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Using qualitative research methods to improve health care for patients with TB and lung disease. Author(s): Dick J, Buskens I. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2003 April; 7(4): 305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729333&dopt=Abstract

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Utility of high-resolution CT for management of diffuse lung disease: results of a survey of U.S. pulmonary physicians. Author(s): Scatarige JC, Diette GB, Haponik EF, Merriman B, Fishman EK. Source: Academic Radiology. 2003 February; 10(2): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583568&dopt=Abstract

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Validity of the IUATLD (1986) questionnaire in the EGEA study. International Union Against Tuberculosis and Lung Disease. Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy. Author(s): Ravault C, Kauffmann F. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2001 February; 5(2): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11258514&dopt=Abstract

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Variable morbidity of respiratory syncytial virus infection in patients with underlying lung disease: a review of the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada. Author(s): Arnold SR, Wang EE, Law BJ, Boucher FD, Stephens D, Robinson JL, Dobson S, Langley JM, McDonald J, MacDonald NE, Mitchell I. Source: The Pediatric Infectious Disease Journal. 1999 October; 18(10): 866-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10530581&dopt=Abstract

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Variations in neutrophil count in preterm infants with respiratory distress syndrome who subsequently developed chronic lung disease. Author(s): Kohelet D, Arbel E, Ballin A, Goldberg M. Source: American Journal of Perinatology. 2000; 17(3): 159-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11012141&dopt=Abstract

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Vascular endothelial growth factor in bronchoalveolar lavage from normal subjects and patients with diffuse parenchymal lung disease. Author(s): Meyer KC, Cardoni A, Xiang ZZ. Source: The Journal of Laboratory and Clinical Medicine. 2000 April; 135(4): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10779049&dopt=Abstract

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Ventilation in the patient with unilateral lung disease. Author(s): Thomas AR, Bryce TL. Source: Critical Care Clinics. 1998 October; 14(4): 743-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891636&dopt=Abstract

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Ventilation of patients with asthma and obstructive lung disease. Author(s): Jain S, Hanania NA, Guntupalli KK. Source: Critical Care Clinics. 1998 October; 14(4): 685-705. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891633&dopt=Abstract

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Very-low-birthweight infants at seven years: an assessment of the health and neurodevelopmental risk conveyed by chronic lung disease. Author(s): Farel AM, Hooper SR, Teplin SW, Henry MM, Kraybill EN. Source: Journal of Learning Disabilities. 1998 March-April; 31(2): 118-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9529782&dopt=Abstract

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Video-assisted thoracoscopic lung biopsy in the diagnosis of diffuse interstitial lung disease. A prospective study. Author(s): Ayed AK. Source: The Journal of Cardiovascular Surgery. 2003 February; 44(1): 115-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627082&dopt=Abstract

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Video-assisted thoracoscopic surgery in the diagnosis of lung disease. The Cretan experience. Author(s): Petrakis IE, Katsamouris A, Vassilakis SJ, Vrachassotakis N, Drossitis I, Chalkiadakis G. Source: Ann Chir Gynaecol. 2000; 89(1): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10791641&dopt=Abstract

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Videothoracoscopic lung biopsy in the diagnosis of interstitial lung disease. Author(s): Rena O, Casadio C, Leo F, Giobbe R, Cianci R, Baldi S, Rapellino M, Maggi G. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1999 December; 16(6): 624-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10647831&dopt=Abstract

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Weaning to extubation directly from high-frequency oscillatory ventilation in an infant with cystic lung disease and persistent air leak: a strategy for lung protection. Author(s): Seller L, Mullahoo K, Liben S, Lands LC. Source: Respiratory Care. 2001 March; 46(3): 263-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11262553&dopt=Abstract

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What does mucin have to do with lung disease? Author(s): Voynow JA. Source: Paediatric Respiratory Reviews. 2002 June; 3(2): 98-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297054&dopt=Abstract

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What is the role of tests of lung function in the management of infants with lung disease? Author(s): Godfrey S, Bar-Yishay E, Avital A, Springer C. Source: Pediatric Pulmonology. 2003 July; 36(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772216&dopt=Abstract

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When and how to assess quality of life in chronic lung disease. Author(s): Janssens JP. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2001 November 10; 131(43-44): 623-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835109&dopt=Abstract

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Winter viruses: influenza- and respiratory syncytial virus-related morbidity in chronic lung disease. Author(s): Griffin MR, Coffey CS, Neuzil KM, Mitchel EF Jr, Wright PF, Edwards KM. Source: Archives of Internal Medicine. 2002 June 10; 162(11): 1229-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038940&dopt=Abstract

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Workshop on lung disease and the environment: where do we go from here? Author(s): Crapo JD, Broaddus VC, Brody AR, Malindzak G, Samet J, Wright JR; American Thoracic Society. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 15; 168(2): 250-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851246&dopt=Abstract

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Worsening of V'maxFRC in infants with chronic lung disease in the first year of life: a more favorable outcome after high-frequency oscillation ventilation. Author(s): Hofhuis W, Huysman MW, van der Wiel EC, Holland WP, Hop WC, Brinkhorst G, de Jongste JC, Merkus PJ. Source: American Journal of Respiratory and Critical Care Medicine. 2002 December 15; 166(12 Pt 1): 1539-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12471071&dopt=Abstract

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CHAPTER 2. NUTRITION AND LUNG DISEASE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and lung disease.

Finding Nutrition Studies on Lung Disease The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “lung disease” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “lung disease” (or a synonym): •

Anti-inflammatory approaches to the treatment of cystic fibrosis lung disease: past, present and future. Author(s): Pediatric Pulmonology Service, Baylor College of Medicine, TCH Feigin Center, Houston, TX, 77030 USA. [email protected] Source: Oermann, C M Curr-Opin-Investig-Drugs. 2001 July; 2(7): 900-6 1472-4472

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Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases. Author(s): Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Medical and Research Center, Denver, CO 80206, USA. [email protected] Source: Maier, L A J-Thorac-Imaging. 2002 October; 17(4): 273-84 0883-5993

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Diet and obstructive lung diseases. Author(s): Pan American Health Organization and National Institute of Public Health, Center for Population Studies, Cuernavaca, Morelos, Mexico. [email protected] Source: Romieu, I Trenga, C Epidemiol-Revolume 2001; 23(2): 268-87 0193-936X

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Drug-induced infiltrative lung disease. Author(s): Service de Pneumologie et de Reanirnation Respiratoire, Centre Hospitalier Universitaire de Dijon, Universite de Bourgogne, France. Source: Camus, P H Foucher, P Bonniaud, P H Ask, K Eur-Respir-J-Suppl. 2001 September; 32: 93s-100s 0904-1850

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Eosinophilic lung disease under chemotherapy with oxaliplatin for colorectal cancer. Author(s): Department of Pulmonary Medicine, Hopital Saint-Antoine, Paris, France. Source: Gagnadoux, Frederic Roiron, Cecile Carrie, Emmanuelle Monnier Cholley, Laurence Lebeau, Bernard Am-J-Clin-Oncol. 2002 August; 25(4): 388-90 0277-3732

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Establishing normal values for nickel in human lung disease. Author(s): Falconbridge A/S, P. O. Box 604, N-4606 Kristiansand S, Norway. Source: Andersen, I Svenes, K J-Environ-Monit. 1999 December; 1(6): 553-5 1464-0325

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Fibroblast mitogenic activity of lung lavage fluid from infants with chronic lung disease of prematurity. Author(s): Department of Child Health, University of Leicester, Leicester LE2 7LX, UK. Source: Currie, A E Kelly, M Vyas, J R Pandya, H Field, D Kotecha, S Arch-Dis-ChildFetal-Neonatal-Ed. 2002 May; 86(3): F193-7 1359-2998

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Hard metal interstitial lung disease: high-resolution computed tomography appearance. Author(s): Thoracic Imaging Section, Department of Radiology, San Francisco General Hospital, University of California, San Francisco, CA 94110, USA. [email protected] Source: Gotway, M B Golden, J A Warnock, M Koth, L L Webb, R Reddy, G P Balmes, J R J-Thorac-Imaging. 2002 October; 17(4): 314-8 0883-5993

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Monitoring cardiovascular function in infants with chronic lung disease of prematurity. Author(s): Department of Pediatrics, B-395, The Children's Hospital, 1056 E, Denver, CO 80218, USA. [email protected] Source: Abman, S H Arch-Dis-Child-Fetal-Neonatal-Ed. 2002 July; 87(1): F15-8 1359-2998

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Nebulised morphine for severe interstitial lung disease. Author(s): Istituto Malattie Apparato Respiratorio, University of Catania, Via Passo Gravina 187, Catania, Italy. [email protected] Source: Polossa, R Simidchiev, A Walters, E H Cochrane-Database-Syst-Revolume 2002; (3): CD002872 1469-493X

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Pergolide-induced lung disease in patients with Parkinson's disease. Author(s): Academic Department of Medicine, University of Hull, Castle Hill Hospital, Castle Road, Cottingham, East Yorkshire, U.K. Source: Kastelik, J A Aziz, I Greenstone, M A Thompson, R Morice, A H Respir-Med. 2002 July; 96(7): 548-50 0954-6111

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to lung disease; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html

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Minerals L-carnitine Source: Healthnotes, Inc.; www.healthnotes.com

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Food and Diet Fasting Diet Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. DISSERTATIONS ON LUNG DISEASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to lung disease. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “lung disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lung disease, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Lung Disease ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to lung disease. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Airway Liquid Secretion and Its Inhibition: Possible Relevance to Cystic Fibrosis Lung Disease by Trout, Laura; Phd from University of South Alabama, 2003, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3078583

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An Esr Spin Trapping Study on the Role of Free Radicals, Glutathione and Vitamin E in 3-methylindole-induced Lung Disease by Kubow, Stanley Jan; Phd from University of Guelph (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65604

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Digging Our Own Graves: Coal Miners and the Struggle over Black Lung Disease by Smith, Barbara Ellen, Phd from Brandeis University, 1981, 643 pages http://wwwlib.umi.com/dissertations/fullcit/8126895

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Mechanisms of Polyisocyanate-induced Lung Disease by Lee, Chun-ting; Phd from Tulane University, 2002, 160 pages http://wwwlib.umi.com/dissertations/fullcit/3084082

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Pulmonary Disease in Scleroderma: Combined Interstitial Lung Disease and Pulmonary Hypertension and Predictors of Pulmonary Hypertension by Chang, Betty; Phd from The Johns Hopkins University, 2003, 72 pages http://wwwlib.umi.com/dissertations/fullcit/3068129

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Studies on the Pathogenesis of Neonatal Chronic Lung Disease by Sweet, David Gordon; Md from Queen's University of Belfast (united Kingdom), 2002, 205 pages http://wwwlib.umi.com/dissertations/fullcit/f807185

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The Effects of Aerobic and Ventilatory Muscle Training on Pulmonary Function and Submaximal Work Performance in Subjects with Pre-clinical Chronic Obstructive Pulmonary Disease (lung Disease) by Kramer, Peter George, Edd from The University of Tennessee, 1984, 101 pages http://wwwlib.umi.com/dissertations/fullcit/8421393

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The Transtheoretical Model: a Comparison of Stage-specific and Stage-generic Interventions for Exercise Behavior among People with Chronic Lung Disease by Mccleery, Mary Beth; Phd from Kent State University, 1999, 140 pages http://wwwlib.umi.com/dissertations/fullcit/9939723

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 4. CLINICAL TRIALS AND LUNG DISEASE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning lung disease.

Recent Trials on Lung Disease The following is a list of recent trials dedicated to lung disease.8 Further information on a trial is available at the Web site indicated. •

Evaluation and Treatment of Patients with Lung Disease not Participating in Research Condition(s): Lung Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study was developed in order for the professional-staff at the Pulmonary-Critical Care Medical Branch (PCCMB) of the National Heart, Lung, and Blood Institute to maintain their skills and increase their understanding of lung diseases. The study will permit PCCMB staff members to evaluate and treat patients with lung disease who do not meet the criteria for other research studies. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001621

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Evaluation of the Causes and Disease Processes of Chronic Lung Disease Condition(s): Lung Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)

8

These are listed at www.ClinicalTrials.gov.

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Purpose - Excerpt: Chronic lung diseases are disorders associated with abnormalities in any of the structures involved in the process of breathing and bringing oxygen into the lungs and blood. This includes abnormalities in the airways, lungs, blood vessels in and around the lungs, and the tissue covering the lungs (pleura). The purpose of this research study is to evaluate patients referred to the Pulmonary-Critical Care Medicine Branch (P-CCMB) of the National Heart, Lung, and Blood Institute (NHLBI) in order to; 1. Develop a better understanding of the causes and disease processes involved in disorders of the lungs 2. Identify patients eligible to participate in other P-CCMB research studies Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001183 •

Genetic Mechanisms of Chronic Obstructive Pulmonary Disease (COPD) Condition(s): Chronic Obstructive Lung Disease Study Status: This study is currently recruiting patients. Sponsor(s): Department of Veterans Affairs Medical Research Service Purpose - Excerpt: The purpose of this study is to determine whether genetic factors contribute to an individuals risk of developing obstructive lung disease from smoking cigarettes. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018408

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Identification of Genes Associated with Lung Disease in Patients with Rheumatoid Arthritis Condition(s): Healthy; Pulmonary Fibrosis; Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Pulmonary fibrosis (PF) is a condition in which the lungs of a patient become scarred and fibrous. It has been known to occur in as many as 40% of patients diagnosed with rheumatoid arthritis (RA). The cause of the pulmonary fibrosis in patients with RA is unknown. Data gathered from previous research studies suggest that genetics may play a role in the development of PF in patients with rheumatoid arthritis. However, the actual genetic factors involved in the disease process have not been identified. The goal of this study is to identify the genetic markers in patients with pulmonary fibrosis and rheumatoid arthritis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001885

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Inhaled NO for the Prevention of Chronic Lung Disease Condition(s): Lung Diseases; Bronchopulmonary Dysplasia Study Status: This study is currently recruiting patients.

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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether or not inhaled nitric oxide (NO) safely decreases the incidence of chronic lung disease in premature infants. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006401 •

Inhaled NO in Prevention of Chronic Lung Disease Condition(s): Bronchopulmonary Dysplasia; Lung Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test the hypothesis that low-dose inhaled nitric oxide administered to preterm infants who continue to require mechanical ventilation at 14 days of age will reduce the incidence of chronic lung disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000548

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Lung Disease Associated with Rheumatoid Arthritis Condition(s): Pulmonary Fibrosis; Rheumatoid Arthritis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Pulmonary fibrosis (PF) is a condition in which the lungs of a patient become scarred and fibrous. It has been known to occur in as many as 40% of patients diagnosed with rheumatoid arthritis (RA). The cause of the pulmonary fibrosis in patients with RA is unknown. Patients participating in this study will undergo a series of tests and examinations before and throughout the study. The tests include blood and urine tests, electrical measures of heart function (ECG), chest x-rays, CAT scans, nuclear medicine scans, breathing tests, exercise tests, and fiberoptic bronchoscopy. The goals of this study are to: 1. Estimate how common pulmonary fibrosis is in patients with rheumatoid arthritis, 2. Describe the natural course of pulmonary fibrosis in patients with rheumatoid arthritis, 3. Estimate the survival rate of patients with pulmonary fibrosis and rheumatoid arthritis, and 4. Learn more about the factors that contribute to the development or progression fibrotic lung disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001876

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Role of Genetic Factors in the Development of Lung Disease Condition(s): Alpha 1 Antitrypsin Deficiency; Cystic Fibrosis; Lung Disease; Obstructive Lung Disease; Sarcoidosis; Asthma

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Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study is designed to evaluate the genetics involved in the development of lung disease by surveying genes involved in the process of breathing and examining the genes in lung cells of patients with lung disease. The study will focus on defining the distribution of abnormal genes responsible for processes directly involved in different diseases affecting the lungs of patients and healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001532 •

Scleroderma Lung Study Condition(s): Lung Diseases; Pulmonary Fibrosis; Systemic Scleroderma; Scleroderma, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the efficacy and safety of cyclophosphamide versus placebo for the prevention and progression of symptomatic pulmonary disease in patients with systemic sclerosis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004563

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Segmental Bronchoalveolar Lavage Condition(s): Asthma; Chronic Obstructive Airway Disease; Healthy; Lung Disease; Pulmonary Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Bronchoalveolar lavage is a diagnostic and therapeutic procedure conducted by placing a fiberoptic scope into the lung of a patient, and injecting sterile water (saline) into the lung and removing. The sterile water removed contains secretions, cells, and protein from the lower respiratory tract. This sample can be analyzed to provide more information about possible disease processes going on in the lungs. This protocol will be used to perform BAL, bronchial brushing, and bronchial wall biopsy in normal volunteers. The samples collected during the study will be used to examine biochemical processes in the lung that may contribute to lung disease Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001618

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Study of INS37217 Inhalation Solution in Mild to Moderate Cystic Fibrosis Lung Disease Condition(s): Cystic Fibrosis Study Status: This study is currently recruiting patients. Sponsor(s): Inspire Pharmaceuticals; Cystic Fibrosis Foundation Therapeutics Purpose - Excerpt: The purpose of this study is to assess the safety and effectiveness of multiple dosages of INS37217 compared to placebo over 28 days in subjects with mild to moderate cystic fibrosis (CF) lung disease. Study drug will be administered through a nebulizer (a device that delivers medication as a mist by breathing it in). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056147

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Study of the Disease Process of Lymphangioleiomyomatosis Condition(s): Leiomyomatosis; Lung Disease; Pneumothorax; Tuberous Sclerosis Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Pulmonary lymphoangioleiomyomatosis (LAM) is a destructive lung disease typically affecting women of childbearing age. Currently, there is no effective therapy for the disease and the prognosis is poor. This study is designed to determine the disease processes involved at the level of cells and molecules, in order to develop more effective therapy. Researchers plan to identify the proteins and factors that contribute to lung destruction by using bronchoalveolar lavage and lung biopsy to collect samples from the involved lung. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001465

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Yoga for Treating Shortness of Breath in Chronic Obstructive Pulmonary Disease (COPD) Condition(s): Pulmonary Disease, Chronic Obstructive; Lung Diseases, Obstructive; Pulmonary Emphysema; Chronic Bronchitis Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to evaluate the safety and effectiveness of yoga in reducing shortness of breath in people with chronic obstructive pulmonary disease (COPD). Patients in this study must have moderate to severe COPD and be primarily limited by shortness of breath. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051792

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Assessing the Occupation Burden in COPD Condition(s): Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To assess the population burden of occupational exposures in the prevalence and progression of chronic obstructive pulmonary disease (COPD). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006513

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Chronic Obstructive Pulmonary Disease Gene Localization Condition(s): Lung Diseases; Chronic Obstructive Pulmonary Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To localize within the genome a chronic obstructive pulmonary disease susceptibility gene. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037739

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Diet and Chronic Obstructive Pulmonary Disease Condition(s): Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the relationship of specific dietary factors to risk of chronic obstructive pulmonary disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006419

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Gene Modifiers in Cystic Fibrosis Lung Disease Condition(s): Cystic Fibrosis; Lung Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine genetic modifiers of the severity of cystic fibrosis lung disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037765

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Lung Health Study (LHS) I and III Condition(s): Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: In the Lung Health Study I, to determine the effects of Special Care, compared to Usual Care, on rate of decline in pulmonary function in a group of cigarette smokers identified as having mild abnormalities in pulmonary function. In the Lung Health Study III, to determine the long-term effects of smoking cessation and continued smoking, on cardiopulmonary morbidity, mortality, and the rate of decline in the one second forced expiratory volume (FEV1) in men and women with early chronic obstructive lung disease who have been followed prospectively for 12 to 15 years. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000568

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Risk Factors in Bronchopulmonary Dysplasia (Newborn Lung Project) Condition(s): Bronchopulmonary Dysplasia; Lung Diseases; Respiratory Distress Syndrome Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate risk factors in bronchopulmonary dysplasia (BPD) and to elucidate the relationship between BPD, acute lung disease severity, respirationrelated variables, water balance, nutrition, familial predisposition, and environmental, pregnancy, and delivery parameters. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005289

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Characterization of the Pathobiology of Early Lung Destruction in Alpha 1Antitrypsin Deficient Individuals Condition(s): Emphysema; Lung Diseases, Obstructive; alpha 1-Antitrypsin Deficiency Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Alpha 1-antitrypsin-deficient individuals develop severe destructive lung disease much earlier and their lung function declines faster than the general population of individuals with chronic obstructive lung disease. This study is designed to better understand the pathogenesis of lung destruction in alpha 1-antitrypsin deficient individuals and to characterize the pathobiology of early lung destruction. To accomplish this we intend to use bronchoalveolar lavage to determine and quantify the factors that initiate and sustain lung inflammation in alpha 1-antitrypsin deficient individuals with lung function above a force expiratory volume in one second (FEV1) of greater than 50% of predicted.

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Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001462 •

Clinical Interventions in Respiratory Distress Syndrome and Neonatal Lung Injury SCOR in Lung Biology and Diseases in Infants and Children Condition(s): Lung Diseases; Respiratory Distress Syndrome; Bronchopulmonary Dysplasia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct clinical interventions directed at neonatal lung disease and injury, with a focus on infants having surfactant-deficiency or inactivation as a component of pathophysiology. A major emphasis was on the surfactant-deficient Respiratory Distress Syndrome (RDS) of premature infants, and on acute neonatal respiratory failure in term infants with pulmonary edema and potential surfactant inactivation (ARDS-related). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005683

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Clinical Study of Intermittent Positive Pressure Breathing (IPPB) Condition(s): Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the efficacy of long-term intermittent positive pressure breathing (IPPB) treatment when used as an adjunct to the overall care of ambulatory outpatients with chronic obstructive pulmonary disease. The evaluation compared the use of IPPB with use of a powered nebulizer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000565

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Developmental Sequelae of Severe Chronic Lung Disorders Condition(s): Bronchopulmonary Dysplasia; Lung Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the impact of bronchopulmonary dysplasia (BPD) on childhood development, family functioning, and parental stress. Study Type: Observational Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00005294 •

Diffuse Fibrotic Lung Disease Condition(s): Lung Diseases; Pulmonary Fibrosis; Sarcoidosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effects of cyclophosphamide compared with prednisone, dapsone, or high-dose intermittent 'pulse' therapy with methylprednisolone in patients with idiopathic pulmonary fibrosis. Also, to evaluate the use of intermittent, short-term, high-dose intravenous corticosteroids in patients with sarcoidosis. There were actually four separate clinical trials. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000596

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Early Risk Predictors For Chronic Pulmonary Disease Condition(s): Asthma; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To continue to evaluate risk factors heretofore determined to be important predictors of chronic respiratory symptoms, diagnosis of asthma, and alterations in expected levels of lung function in children and adolescents in a new population of young adult women. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005281

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Effectiveness and Cost Impact of a Telecommunications System in COPD Condition(s): Lung Diseases, Obstructive Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the adult population, and accounts for approximately 25,000 discharges from VA hospitals in a calendar year. Interventions that enhance symptom self-monitoring and increase understanding of COPD therapy may reduce the occurrence of COPD-related hospitalizations and other acute health care services. However, such interventions are labor-intensive and expensive, and typically require patients to go to a medical facility on a regular basis. A novel means of providing such interventions is the Telephone-Linked Computer (TLC) system, a computer-based telecommunications system that can monitor, educate, and counsel patients through regular automated conversations in patients? homes. In previous studies, we have

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demonstrated the applicability of TLC technology in the clinical monitoring of adults with chronic disease conditions such as hypertension and hypercholesterolemia. The overall goal of this project is to determine whether a TLC system for COPD care (TLCCOPD) leads to a reduction in emergency department (ED) visits and hospitalizations and to improved functional status and quality of life (QOL) in patients with COPD. The following specific objectives will be accomplished: (1) test the hypothesis that the addition of TLC-COPD to usual medical care reduces the use of acute health care services over a one-year follow-up period; (2) test the hypothesis that TLC-COPD use leads to improvements in functional status and QOL; (3) test the hypothesis that the reduction in the cost of care over the one-year follow-up period will exceed the cost of the TLC intervention; and (4) test the hypothesis that the TLC-COPD is cost effective compared with usual care in achieving improvements in functional status and QOL. Hypotheses will be tested by means of a randomized controlled trial involving subjects with COPD who receive care at two Boston-area VA hospitals. Subjects will be assigned to either TLC-COPD or a usual care control group. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012805 •

Emphysema: Physiologic Effects of Nutritional Support Condition(s): Emphysema; Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if enteral nutrition support (ENS) restores normal body weight and improves muscle strength, exercise performance, sensation of dyspnea, and quality of life in malnourished patients with chronic obstructive pulmonary disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000573

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Epidemiology of Airway Responsiveness Condition(s): Asthma; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To prospectively identify factors that influence the rate of decline in pulmonary function and to identify predictors of chronic obstructive lung disease (COLD) and asthma in a population sample of older adults. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005284

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Epidemiology of Interstitial Lung Disease Condition(s): Lung Diseases; Lung Diseases, Interstitial Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To establish a population-based registry of interstitial lung disease in Bernalillo County, New Mexico. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005290

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Genetics of Airway Responsiveness and Lung Function Condition(s): Asthma; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To perform a genome-wide search for genes affecting two phenotypes related to asthma and chronic obstructive pulmonary disease (COPD) in a Chinese population. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005537

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Idiopathic Pulmonary Fibrosis--Pathogenesis and Staging - SCOR in Occupational and Immunological Lung Diseases Condition(s): Lung Diseases; Scleroderma, Systemic

Pulmonary

Fibrosis;

Lung

Diseases,

Interstitial;

Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct cross-sectional and longitudinal studies of patients with idiopathic pulmonary fibrosis (IPF) and patients with progressive systemic sclerosis (PSS), with and without associated lung disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005317 •

Inhaled Beclomethasone to Prevent Chronic Lung Disease Condition(s): Bronchopulmonary Dysplasia; Hyaline Membrane Disease; Lung Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test if inhaled glucocorticoids, early in the course of respiratory failure in premature infants, permit normal lung growth and differentiation, thus preventing development of bronchopulmonary dysplasia.

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Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000576 •

Lung Health Study II Condition(s): Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if participants with chronic obstructive pulmonary disease, who were assigned to inhaled corticosteroids had a lower rate of decline in lung function and lower incidence of respiratory morbidity compared to participants assigned to placebo. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000569

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Minimal Breathing Support and Early Steroids to Prevent Chronic Lung Disease in Extremely Premature Infants (SAVE) Condition(s): Bronchopulmonary Dysplasia; Respiratory Distress Syndrome; Infant, Premature, Diseases Study Status: This study is terminated. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Preterm birth is a common cause of neonatal morbidity and mortality, including chronic lung disease. Extremely premature newborns who required oxygen and a ventilator for lung disease were randomized to a low tapering dose of corticosteroids vs salt water AND minimal mechanical breathing support vs routine mechanical breathing support for 10 days to test whether either intervention would reduce the risk of death or lung problems. The infants' neurodevelopment will be evaluated at 18 to 22 months corrected age. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005777

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Nocturnal Oxygen Therapy Condition(s): Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)

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Purpose - Excerpt: To compare the efficacy of long-term use of nocturnal oxygen therapy (12 hours) with that of continuous, low-flow oxygen therapy (24 hours) in patients with chronic hypoxic lung disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000564 •

Popcorn Lung: the discovery of a new disease Condition(s): Lung Diseases, Interstitial; Bronchiolitis Obliterans Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: Recently, an epidemic of pulmonary disease has been recognized among workers in a popcorn factory in Jasper, Missouri. The exposure agent has not yet been identified, but suspects include butter flavoring and the powdered salt used in the mixing room. This disease resembles "Bronchiolitis Obliterans Syndrome", an illness that makes it difficult to breathe. Of the 117 workers studied, one year later, 25 subjects whom were working in the mixing room or in the microwave packaging area have had decreases in lung function seven times the norm for their age. Industrial hygiene experts revealed that dust concentrations of salt and other flavorings were much higher in the mixing room compared to the office and outdoor work areas. Recently, rats were exposed to vapors created by heating the butter flavor compound obtained from this plant. Six-hour exposure to vapors at very high concentration resulted in significant damage to the breathing apparatus. Thus, there is clinical, epidemiological, and animal toxicity data that appears to implicate some constituent present during the mixing of the butter flavoring, salt, and oil causing a form of obstructive airway disease that has been rapidly progressive in a number of workers. It is not clear what the pathophysiologic nature of this entity is, though it resembles Bronchiolitis Obliterans Syndrome. It is not known what the long term consequence of this will be on the active workers, nor is it clear whether preventive measures taken to reduce exposures in the mixing room and elsewhere in the plant are going to be effective. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00027235

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Randomized Controlled Trial of Exercise Training in Patients with COPD Condition(s): Lung Diseases, Obstructive Study Status: This study is completed. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Health Services Research and Development Service Purpose - Excerpt: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the adult population, and accounts for approximately 25,000 discharges from VA hospitals in a calendar year. In addition to the burden put on the health care system, COPD is a disabling condition that adversely affects functional status and quality of life (QOL). Several reports have suggested that exercise training programs can reduce the frequency of hospitalization for COPD; however, these reports

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have important methodologic limitations, and such programs have not been widely implemented in the VA health care system. Although the underlying lung pathology of COPD may be unalterable, physical reconditioning has been clearly demonstrated to improve cardiorespiratory status in COPD patients. These physiologic changes have the potential to substantially improve QOL and reduce functional disability. Moreover, improved cardiorespiratory reserve may decrease the utilization of health care resources during mild to moderate exacerbation of COPD. The overall goal of this project is to determine whether exercise training leads to a reduction in chronic institutionalization, acute hospitalization, and outpatient physician visits and to improved functional status and QOL in patients with COPD. The following specific objectives will be accomplished: (1) test the hypothesis that the addition of exercise training to usual care reduces use of health care services over a one-year follow-up period; and (2) test the hypothesis that exercise training leads to improvements in functional status and QOL. Hypotheses will be tested by means of a randomized controlled trial involving subjects with COPD (aged 50-79 years) who receive care at two Boston area VA hospitals. Subjects randomized to the intervention group will receive an eight-week program of thrice-weekly exercise training sessions. Outcomes will include a standardized QOL questionnaire and objective tests of functional status (6-minute walk and activities of daily living performance). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012792 •

Specialized Center of Research in Occupational and Immunologic Lung Disease Condition(s): Lung Diseases, Obstructive; Asbestosis; Silicosis; Pneumoconiosis; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The overall objective of the Center was to develop a scientific data base for the control and prevention of acute and chronic lung injury caused by the inhalation of a variety of agents in the workplace and in the environment. There were two epidemiologic studies. Respiratory Effects of Exposures to Irritant Gases: To collect longitudinal lung function and symptom data in chemical manufacturing workers who were exposed to chemical irritants such as ammonia, chlorine, phosgene, isocyanates, sulphur dioxide, nitrous oxide, formaldehyde, organic acids, hydrochloric acid fluorides, other aldehydes, and acid anhydrides. Workers in the Cotton Textile Industry: To detect and quantitate the risk for the development of chronic obstructive airways disease which occurred in workers exposed to cotton dust in textile manufacturing. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005280

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Statistical Analysis of Vlagtwedde-Vlaardingen Data Set Condition(s): Asthma; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease

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Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the effects in early adulthood of asthma, increased bronchial responsiveness, markers of allergy and smoking on pulmonary function level and the effects of these same risk factors on subsequent decline in pulmonary function, because these early adult factors presumably profoundly influence the risk for chronic obstructive pulmonary disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005425 •

Trial of Inspiratory Muscle Rest and Exercise in Chronic Obstructive Lung Disease Condition(s): Lung Diseases; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test the effectiveness of ventilatory muscle rest (VMR) using home negative pressure ventilation (NPV) in improving exercise performance, alleviating dyspnea, and improving the quality of life in patients with severe chronic obstructive lung disease. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000571

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Tucson Epidemiology Study of Chronic Obstructive Lung Diseases Condition(s): Asthma; Bronchitis; Emphysema; Lung Diseases, Obstructive; Chronic Obstructive Pulmonary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the natural history, etiology, and interrelationships of emphysema, chronic bronchitis, asthma, and related airways obstructive diseases. Also, to determine the relationship of acute lower respiratory tract illnesses in infants and children to the development of subsequent chronic lung disorders. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005279

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Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “lung disease” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON LUNG DISEASE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “lung disease” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lung disease, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Lung Disease By performing a patent search focusing on lung disease, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on lung disease: •

2-Substituted-1-naphthols as 5-lipoxygenase inhibitors Inventor(s): Batt; Douglas G. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,906,636 Date filed: March 16, 1989 Abstract: 2-Substituted-1-naphthols are 5-lipoxygenase inhibitors which make them useful in the treatment of inflammation, obstructive lung disease and/or psoriasis. Useful 2-substituent groups are alkyls, alkenyls, alkynyls, cycloalkyls, cycloalkenyls, the groups CH.sub.2 --C.tbd.C--(CH.sub.2).sub.m R.sup.5 and CH.dbd.CH-(CH.sub.2).sub.n R.sup.5 (where m is 1-4, n is 0-3 and R.sup.5 includes phenyl, COOR.sup.9, where R.sup.9 is H or alkyl or 1-4 carbons, AR.sup.6 (where A is a methylene chain and R.sup.6 is a variety of groups including Cl, Br, I, CHO, CN, COOR.sup.9, NH.sub.2, SC(NH)NH.sub.2, phenyl, P(O)(OR.sup.9).sub.2, etc.), and CHR.sup.7 R.sup.21 (where R.sup.7 is a variety of aromatic and heterocyclic groups and R.sup.21 is H, optionally substituted phenyl and a variety of heterocyclic groups). Excerpt(s): This invention relates to 2substituted-1-naphthols, and processes for their preparation, pharmaceutical compositions containing them and pharmaceutical methods using them. U.S. Pat. No. 3,998,966 issued Dec. 21, 1976 to Fried and Harrison discloses 6-substituted 2-naphthyl acetic acid derivatives with antiinflammatory, analgesic, antipyretic and antipruritic activity. A number of references disclose 1naphthol as a lipoxygenase inhibitor, including T. Nakadate et al., Gann, 75, 214 (1984); J. Van Wauwe and J. Goossens, Prostaglandins, 26, 725 (1983); and R. V. Panganamala et al., Prostaglandins, 14, 261 (1977). Web site: http://www.delphion.com/details?pn=US04906636__

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Apparatus for conservative supplemental oxygen therapy Inventor(s): Blum; Alvin S. (2350 Del Mar Pl., Fort Lauderdale, FL 33301) Assignee(s): none reported Patent Number: 4,584,996 Date filed: March 12, 1984 Abstract: Method and apparatus for intermittent administration of supplemental oxygen to patients with chronic obstructive lung disease. The apparatus is programmable for the specific oxygen requirements of the patient and is responsive to changes in requirements with increased patient activity. Patient's arterial blood oxygen level is measured while supplying oxygen to determine the number of respiratory cycles required to reach a first desired arterial blood oxygen level and it is again measured without supplemental oxygen to determine the number of respiratory cycles required to diminish to a second, lower particular level. These two cycle numbers are applied as a program to apparatus having respiratory cycle sensing and counting and control valve means to provide a regulated flow of supplemental oxygen to a nasal cannula for a predetermined number of on respiratory cycles and to shut off the flow for a preset number of off respiratory cycles sequentially and repetitively. The oxygen conservation

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properties are further enhanced by turning off the oxygen flow during the exhalation phase of each respiratory cycle throughout the on respiratory cycles. As the respiratory rate increases with activity, the duration of the on and off periods thereby changes accordingly. Performance may be further enhanced by means changing the programmed cycle numbers and ON/OFF intervals in response to changes in the respiratory rate. Excerpt(s): This invention relates to systems for supplying supplemental oxygen to a patient intermittently with the supply on for a predetermined number of ON respiratory cycles and the supply off for a predetermined number of OFF respiratory cycles. Oxygen saving is further enhanced by shutting the oxygen flow off during the exhalation phase of each ON respiratory cycle. The incidence of chronic obstructive lung disease (C.O.L.D.) is increasing. These patients have inadequate pulmonary gas exchange resulting in inadequate oxygenation of blood passing through the lungs. Inadequate blood oxygenation and consequent body tissue hypoxia account for the disabling effects of the disease. It has been demonstrated that continuous administration of supplemental oxygen by nasal cannula overcomes the functional disability and greatly improves the quality of life as well as prolonging life. It is now common practice for ambulatory patients to carry an oxygen supply weighing nine pounds and lasting 3-4 hours. Prior art devices conserve oxygen by shutting off the gas flow during the exhalation phase of each respiratory cycle, which may double the effective supply. Restricted mobility, activity and costs of C.O.L.D. therapy may be effectively reduced by intermittent oxygen therapy. This intermittent oxygen therapy can replace continuous oxygen therapy because of the unusual physiological nature of C.O.L.D. To conserve oxygen, a number of oxygen supply systems turn off the oxygen flow during exhalation and turn on the oxygen flow only during inhalation. It is an object of this invention to further extend and conserve the oxygen supply by turning the oxygen flow off for a predetermined number of OFF respiratory cycles, and then turning the flow on only during inspirations for a predetermined number of ON cycles. When physical exertion increases oxygen requirements, the respiration rate will also increase, thereby shortening the ON/OFF time intervals correspondingly. Alternatively performance may be further enhanced by programmatically changing cycle numbers, flow rates, and ON/OFF intervals in response to respiratory rate. Web site: http://www.delphion.com/details?pn=US04584996__ •

Determination of oxidized.alpha.-1-proteinase inhibitor in serum or plasma Inventor(s): Travis; James (Athens, GA) Assignee(s): University of Georgia Research Foundation, Inc. (Athens, GA) Patent Number: 4,493,891 Date filed: July 27, 1982 Abstract: A new method of determining oxidized.alpha.-1-proteinase inhibitor in serum or plasma for use in studying the development of chronic obstructive lung disease is disclosed. Levels of oxidized.alpha.-1-proteinase inhibitor indicate the potential for emphysema development with higher levels showing a decrease in lung protection against elastolytic enzymes such as elastase. This method can be used for patients with a potential for chronic obstructive lung disease rather than having to use bronchial lavage methods for such patients. No other method is known to exist for determining oxidized.alpha.-1-proteinase inhibitor in serum or plasma.

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Excerpt(s): This invention relates to a method of determining oxidized.alpha.-1proteinase inhibitor in serum or plasma. This method is a diagnostic technique useful in studying the development of chronic obstructive lung disease. More specifically this method is useful for patients having a potential for chronic obstructive lung disease rather than using bronchial lavage methods. No other method is known to exist for determining oxidized.alpha.-1-proteinase inhibitor in serum or plasma. Pulmonary emphysema appears to be a consequence of accelerated lung elastin degradation that results from either an elevated level of elastase activity or a decreased level of elastase inhibitor(s) within the lung, or a combination of both factors. Neutrophil elastase is probably the major elastolytic activity involved in development of emphysema although elastase activity from other sources such as macrophages and monocytes may have a role. The principal inhibitor of neutrophil elastase is the plasma protein.alpha.-1proteinase inhibitor (formerly referred to as.alpha.-1-antitrypsin). Severe genetic deficiencies of this protein commonly result in emphysema in the affected individuals.alpha.-1-proteinase prevents the accumulation of leukocytes which contain proteases such as elastase within their cytoplasmic granules. Most smokers who develop emphysema do so despite normal levels of.alpha.-1-proteinase inhibitor. An explanation for emphysema in smokers with normal.alpha.-1-proteinase inhibitor concentrations has evolved from the observation of the ease of oxidation of the reactive site methionyl residue of this protein leading to a two-thousand fold reduced rate of association of the oxidized inhibitor with human leukocyte elastase. Thus, reduced levels of elastase inhibitory activity can result from partial oxidation of the.alpha.-1-proteinase inhibitor in the lung through inhalation of oxidants present in tobacco smoke, ozone, or industrial gases, as well as from oxidants released from cells in the lung, even if levels of plasma.alpha.-1-proteinase inhibitor are normal or elevated. Web site: http://www.delphion.com/details?pn=US04493891__ •

Formulations containing growth hormone and nutritional supplements, and methods of treating malnutrition in chronic lung disease Inventor(s): Rothkopf; Michael (North Caldwell, NJ) Assignee(s): Clinical Homecare, Corp. (Fairfield, NJ) Patent Number: 5,179,080 Date filed: August 31, 1989 Abstract: Methods of treating malnutrition associated with chronic lung diseases comprising the administration of metabolically active peptides in an amount sufficient to increase circulating somatomedin C levels more than 0.8 U/ml plasma above the patient's baseline SmC level, along with nutritional supplementation providing a daily caloric intake of between 100% and 200% of the patient's baseline resting energy expenditure; and formulations utilized therein. Excerpt(s): This invention relates to formulations of metabolically active peptides and nutritional supplements, and to methods of treatment of malnutrition in chronic lung diseases therewith. The present invention is directed to formulations and methods of treating malnutrition associated with chronic lung diseases. Chronic lung diseases include diseases such as chronic obstructive pulmonary disease (COPD), cystic fibrosis and interstitial lung disease. A common characteristic of these diseases is the decreased capacity of lungs to exchange oxygen and carbon dioxide. This causes the patient to breathe faster which increases the energy the patient must expend in order to obtain enough oxygen. Malnutrition is a common complication in these patients resulting from

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the increased energy needed to breathe as well as the reduced oral intake of food. This often results in weight loss which leads to a decline in pulmonary function. Severe weight loss is associated with a poor prognosis and increased mortality. Sukumalchantra, et al. Am. J Med, 39:941-945 (1965); Vandenbergh, et al., Am Rev Respir Dis, 95:556-566 (1967); Burrows, et al., Am Rev Respir Dis. 91:665-678 (1963); and Tiech, S., Chest. 85:635-665(1984). Web site: http://www.delphion.com/details?pn=US05179080__ •

Method of detecting lung disease Inventor(s): Boucher, Jr.; Richard C. (Chapel Hill, NC) Assignee(s): University of North Carolina at Chapel Hill (Chapel Hill, NC) Patent Number: 6,133,247 Date filed: January 22, 1997 Abstract: A method of facilitating the obtaining of a mucus sample from at least one lung of a subject comprises administering to at least one lung of the subject, in an amount effective to hydrate lung mucous secretions and/or stimulate cilia beat frequency therein, uridine 5'-triphosphate, an active analog thereof, or a pharmaceutically acceptable salt of either thereof, and, optionally, concurrently administering to said at least one lung a physiologically acceptable salt in an amount effective to hydrate lung mucus secretions therein. A sputum or mucus sample is then collected from said at least one lung, which sample can then be analyzed for lung disease. Pharmaceutical compositions useful for carrying out the method comprise UTP or a salt thereof, alone or in combination with a physiologically acceptable salt, or a pharmaceutically acceptable salt of either thereof. The composition may be a liquid/liquid suspension composition or a dry powder composition. Excerpt(s): This application concerns lung diagnostic assays in general, and particularly concerns a lung diagnostic assay in which lung mucus secretions are hydrated to facilitate collection thereof. The analysis of sputum samples is particularly important in the treatment and diagnosis of many lung disorders, including lung cancer and tuberculosis (TB). In particular, microbial infections of the lung are a serious problem in patients afflicted with acquired immune deficiency syndrome (AIDS). Two particularly problematic infections are Pneumocystis carinii pneumonia infections and mycobacterial infections. Web site: http://www.delphion.com/details?pn=US06133247__

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Method of treating lung disease with uridine triphosphates Inventor(s): Boucher, Jr.; Richard C. (Chapel Hill, NC) Assignee(s): The University of North Carolina At Chapel Hill (Chapel Hill, NC) Patent Number: 5,292,498 Date filed: June 19, 1991 Abstract: A method of hydrating mucous secretions in the lungs of a subject in need of such treatment is disclosed. The method comprises administering to the lungs of the subject a uridine triphosphate such as uridine 5'-triphosphate (UTP) or uridine 5'-O-(3thiotriphosphate) (UTP.gamma.S) in an amount effective to hydrate lung mucous

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secretions. The method is useful for treating patients aflicted with cystic fibrosis. Pharmaceutical formulations and methods of making the same are also disclosed. Excerpt(s): This invention relates to a method of removing retained mucus secretions from the lungs of a patient by administering certain uridine triphosphates to the lungs of the patient. Extracellular adenosine triphosphate has been shown to regulate a variety of biological processes including non-vascular smooth muscle contraction (M. Maguire and D. Satchell, J. Pharmacol. Exp. Ther. 211, 626-631 (1979); C. Brown and G. Burnstock, Eur. J. Pharmacol. 69, 81-86 (1981)) and vascular tone (G. Burnstock and C. Kennedy, Circ. Res. 58, 319-330 (1986); D. Haeussinger et al., Eur. J. Biochem. 167, 65-71 (1987)), platelet aggregation (G. Born and M. Kratzer, J. Physiol. (Lond.) 354, 419-429 (1984)), neurotransmission (G. Burnstock, Nature, 229, 282-283 (1971); G. Burnstock and P. Sneddon, Clin. Sci. 68 (Suppl. 10), 89s-92s (1985)), and cellular ion transport (G. Burgess et al., Nature 279, 544-546 (1979); D. Galacher, Nature 296, 83-86 (1982)) and secretory activities (J. Chapal and M-M. Loubatieres-Mariani, Br. J. Pharmacol. 73, 105-110 (1981); J. Pearson et al., Biochem. J. 214, 273-276 (1983)). These effects are mediated by specific purinergic receptors which respond to ATP or other nucleotides present in the extracellular millieu (J. Gordon, Biochem. J. 233, 309-319 (1986)). Purinoceptors have been functionally identified in rat pulmonary epithelia in studies of regulation of alveolar Type II surfactant phospholipid secretion (W. Rice and F. Singleton, Br. J. Pharmacol. 89, 485-491 (1986)). To our knowledge these receptors have not been reported in human airway epithelial cells. Because ion transport appears to be regulated by purinergic receptor stimulation in other epithelia (Burgess et al., supra (1979); Gallacher, supra (1982)), we investigated several features of the effect of extracellular nucleotides on the ion transport activities of human airway epithelium. Web site: http://www.delphion.com/details?pn=US05292498__ •

Methods for treating interstitial lung disease by using interleukin-9 and its antagonists Inventor(s): Huaux; Francois (Brussels, BE), Lison; Dominique (Brussels, BE), Many; Mary-Christine (Brussels, BE), Renauld; Jean-Christophe (Brussels, BE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 5,935,929 Date filed: September 8, 1997 Abstract: A method for the treatment and prevention of immune disorders and fibrosis associated disorders is disclosed. The method involves administering interleukin-9 in an effective amount to the subject. Among the conditions treatable are thyroiditis, autoimmune diabetes and silicosis. Excerpt(s): This invention relates to the treatment of pathological conditions which are treatable via administration of interleukin-9 ("IL-9") or interleukin-9 analogs, antagonists, and so forth. In particular, fibrotic, and autoimmune diseases are treatable via administration of IL-9 or its analogs, alone or together with other drugs. Interleukin9 ("IL-9" hereafter), is a glycoprotein which has been isolated from both murine and human cells. See, e.g., U.S. Pat. No. 5,208,218, incorporated by reference. This reference also teaches isolated nucleic acid molecules encoding the protein portion of the molecule, and how to express it. Various uses of the molecule can be seen in, e.g., U.S. Pat. No. 5,164,317 (proliferation of mast cells); U.S. Pat. Nos. 5,246,701 and 5,132,109 (enhancing production of IgG and inhibiting production of IgE), in addition to its first

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recognized utility, which is as a T cell growth factor. Exemplary of the vast scientific literature on the molecule are Van Snick, et al, J. Exp. Med. 169(1): 363-368 (1989) (cDNA for the murine molecule, then referred to as P40). Houssiau, et al, J. Immunol 148(10): 3147-3151 (1992) (IL-2 dependence of IL-9 expression in T lymphocytes). Renauld, et al, Oncogene 9 (5): 1327-1332 (1994) (effect on thymic lymphomas); Renauld, et al, Blood 85(5): 1300-1305 (1995) (anti-apoptotic factor for thymic lymphoma). Review articles may be found at, e.g., Renauld, et al, Cancer Invest 11(5): 635-640 (1993); Renauld, et al, Adv. Immunol 54: 79-97 (1993). Web site: http://www.delphion.com/details?pn=US05935929__ •

Methods of inhibiting phospholipase A2 and phospholipase A2 stimulator activities Inventor(s): Tsao; Francis H. C. (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 6,180,596 Date filed: January 30, 1998 Abstract: A method for inhibiting PLA.sub.2 or suppressing the activity of a PLA.sub.2 stimulator in a body fluid of an animal with lung disease involves adding Annexin I, Annexin VIII or a mixture thereof to the body fluid. Excerpt(s): The present invention generally relates to annexins. More particularly, it relates to methods of inhibiting phospholipase A.sub.2 (PLA.sub.2) and the activity of PLA.sub.2 simulators which employ Annexin I and Annexin VIII. Annexins are a group of calcium-dependent, phospholipid-binding proteins. The calcium and phospholipid binding sites of most annexins are located in four repeated and highly conserved regions each of which contains about 70 amino acids. These proteins are widely distributed and at least nine members of the annexin family of proteins have been identified in mammalian tissues. The lung is rich in annexins. Several members of the annexin family of proteins with apparent molecular weights ranging from about 32 to about 40 kDa have been isolated from lungs of animals. Annexin I, a 36 kD phospholipid binding protein, 36 kDa(PLBP), appears to be the most abundant of the annexin family of proteins. It is present in the lung in greater amounts than the related Annexin VIII, a 33 kDa phospholipid-binding protein, also known as 33 kDa(PLBP). Web site: http://www.delphion.com/details?pn=US06180596__

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Methods of treating lung disease by an aerosol containing benzamil or phenamil Inventor(s): Boucher; Richard C. (Chapel Hill, NC), Stutts; Monroe Jackson (Chapel Hill, NC) Assignee(s): The University of North Carolina at Chapel Hill (Chapel Hill, NC) Patent Number: 5,656,256 Date filed: December 14, 1994 Abstract: Method of hydrating lung mucous secretions in the lungs of a subject are disclosed. The methods involve administering benzamil or phenamil to the lungs of the subject in an amount effective to hydrate lung mucous secretions. The administering step is preferably carried out by inhalation administration. The method is useful in the treatment of diseases such as cystic fibrosis and chronic bronchitis.

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Excerpt(s): These inventions relate to a method of hydrating lung mucous secretions by administering benzamil to the lungs of a subject, and a method of hydrating lung mucous secretions by administering phenamil to the lungs of a subject. In cystic fibrosis several functions of airway epithelia are abnormal, and deficiencies in both CL.sup.transport and Na.sup.+ absorption are well documented. See, e.g. Knowles et al., Science 221, 1067 (1983); Knowles et al., J. Clin. Invest. 71, 1410 (1983). Regulation of ion transport might have potential therapeutic benefit in lung diseases characterized by abnormalities in epithelial ion transport, e.g., cystic fibrosis. One therapeutic goal in cystic fibrosis and other pulmonary diseases in which the water content of the mucous is altered is to hydrate the lung mucous secretions, so that the secretions may be thereafter more easily removed from the lungs by mucociliary action or simple coughing. The use of aerosolized amiloride to hydrate mucous secretions is described in U.S. Pat. No. 4,501,729. Amiloride appears to block Na.sup.+ reabsorption by airway epithelial cells, and therefore inhibits water absorption from the mucous. While an important breakthrough in providing treatments for cystic fibrosis, a potential problem with amiloride treatments is the relatively short duration of action of amiloride. Web site: http://www.delphion.com/details?pn=US05656256__ •

Microporous laminate Inventor(s): Conover; Stephen P. (Minneapolis, MN) Assignee(s): Applied Membrane Technology, Inc. (Minnetonka, MN) Patent Number: 4,444,662 Date filed: October 22, 1979 Abstract: A laminate formed by the solvent casting of a two phase siloxane-polyarylene polyether block copolymer onto a suitable microporous substrate such as a microporous polypropylene film, to produce a gas permeable and blood compatible membrane having sufficient mechanical strength for use in blood oxygenators and gas separation devices. For use in blood oxygenators, implantable biomedical devices, blood sampling, analysis or purification devices and artificial membrane lungs for cancer therapy or lung disease therapy, the two phase block copolymers such as polysufonepolydimethylsiloxane block copolymer preferrably have molecular weights in the ratio 5,000/5,000 M.sub.n 's with a 45% volume fraction as polysulfone, or at least 50% volume fraction represented as siloxane. For use in gas separation devices, the molecular weights of the polysulfone-polydimethylsiloxane blocks may be varied from 1,500 to 100,000 or greater M.sub.n 's with 10 to 90% by weight siloxane, and from 90 to 10% by weight polysulfone, with a tensile modulus less than 100,000 psi and tensile elongation of at least 100%.The process for producing the laminate consists of a meniscus dip coating technique to apply a uniform coating of the polymer to only one side of the microporous substrate in order to maintain coating thickness and to leave the other side uncoated for ease of heat sealing or potting of the membranes together into envelopes. Excerpt(s): This invention relates generally to polymers that can be formed into films, membranes, coatings, fibers, woven and non-woven layers and similar structures, the structures having gas permeability, hydrolytic stability, mechanical strength and blood compatibility and more specifically to the novel formation of supported ultrathin membranes of these polymers to have hydrolytic stability over a wide range of pH, including blood pH of 7.4, and under sterilization conditions of, for example, 100.degree. C. These ultrathin membranes may be used in devices wherein the blood of a living animal comes into contact with a non-living surface and include blood

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oxyhenators, biological implants, catheters, cannulas and other artificial organs, filters, probes and devices for sampling and analysis of blood as well as gas permeability devices. The prior art recognizes the utilization of polymers that can be formed into films, membranes, coating, woven and non-woven layers and similar structures, which structures have blood compatibility, hydrolytic stability and gas permeability. Numerous types of gas permeable membranes for use in gas separation devices, bloodgas exchange devices and methods for preparation of these membranes also exists in the prior art. A publication "Interactions of Materials with Blood" entitled Blood Compatible Synthetic Polymers by S. D. Bruck published in 1974. Web site: http://www.delphion.com/details?pn=US04444662__ •

Non-adjuvenated vaccine Inventor(s): Clancy; Robert L. (Newcastle, AU) Assignee(s): Broncostat Pty. Limited (Perth, AU) Patent Number: 4,873,090 Date filed: November 12, 1986 Abstract: An enteral non-adjuvenated monobacterial vaccine comprising killed bacteria gives a better protection against acute episodes of infection in patients with long term chronic lung disease than a conventional adjuvenated polybacterial vaccine. The bacteria are usually Haemophilus influenza, Streptococcus pneumoniae, Pseudomonas aeruginosa or Staphylococcus aureus. Excerpt(s): The present invention relates to an enteral monobacterial vaccine comprising killed Haemophilus influenza or Streptococcus pneumoniae, a process for the manufacture of such a vaccine and a method of preventing acute mucosal infections in humans having chronic mucosal disease by administering such a vaccine. Acute episodes of bronchitis in cigarette smokers are a major health problem and are in particular a cause of morbidity and mortality with patients with chronic obstructive lung disease (COLD). The upper respiratory tract of these patients is commonly colonised with Haemophilus influenzae and/or Streptococcus pneumoniae, and it has been held that a shift in the shot-bacteria balance favouring infection with these organisms is the immediate cause of acute bronchitis. Children with cystic fibrosis commonly suffer from chronic infection by Pseudomonas aeruginosa and Staphylococcus aureus. Polybacterial vaccines containing a selection of killed bacteria normally associated with infection of the respiratory tract have been available for many years. The polybacterial vaccines contain an adjuvant of conventional type whose function according to established methodology is to enhance the response of the patient to the antigen thereby leading to enhanced immunity. The adjuvant may be a chemical agent. Alternatively, the variety of organisms themselves function in a non-specific way to activate the immune system. Such adjuvant-containing polybacterial vaccine has been commercially available in tablet form for oral digestion. The tablets are enteric coated to allow passage through the stomach, followed by stimulation of gut-associated lymphoid tissue. However, the effectiveness of these polybacterial vaccines has been disappointing in the treatment of acute bacterial infections of the respiratory tract in humans having chronic mucosal inflammations. It is an object of the present invention to provide an enteral vaccine against infections of mucosal surfaces in humans having long term mucosal disease. Web site: http://www.delphion.com/details?pn=US04873090__

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Nutritional product for human infants having chronic lung disease Inventor(s): Benson; John D. (Powell, OH), Breen; Merlin D. (Westerville, OH), Churella; Helen R. (Columbus, OH), Neylan; Michael J. (Worthington, OH), Ostrom; Karin M. (Reynoldsburg, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 5,340,603 Date filed: August 30, 1993 Abstract: A hypercaloric formula providing nutritional support for human infants having chronic lung disease, said formula having a caloric density of at least 800 kcalories per liter of formula and wherein not less than 56% of the total calories in said formula is derived from fat; not more than 15% of total calories is derived from a high quality protein source; and from about 20-27% of total calories is from a carbohydrate source; said formula having a calcium to phosphorous ratio in the range of 1.4 to 2.2, and having an m-inositol concentration of at least 50 milligrams per liter of formula. Excerpt(s): The present invention relates generally to a liquid nutritional product, and more particularly to a nutritional product specially formulated for use in the management of human infants having compromised lung function. During the third trimester of pregnancy, growth of the fetus is greater than at any other time in its development. Of an estimated 4.2 million live births in the United States each year, approximately 383,000 (about 9%) occur prematurely. A low birth-weight infant or any infant born prematurely misses part or all of the critical period of in utero growth, and therefore, would benefit from a nutritional formula that contains greater amounts of nutrients than are found in standard infant formulas or in breast milk in order to support nutrient accretion at the in utero rate leading to growth and development of the infant. Further, a nutritional formula for low birth weight infants must provide these nutrients without disrupting or stressing the physiologic and metabolic systems of the preterm infant that are not yet fully developed. The most common medical problem encountered in the premature infant is respiratory in origin often due to a lack of pulmonary development. For example, respiratory distress syndrome, aspiration syndromes, and pneumonia frequently occur in the first hours of life. As a consequence, these infants suffer from bloodlung gas exchange disorders which most typically result in a blood level of carbon dioxide which is clinically considered too high and an oxygen level which is considered too low. Aggressive medical intervention is required to treat these infants and includes the administration of supplemental oxygen, endotracheal intubation and mechanical ventilation with positive pressure respirators. Web site: http://www.delphion.com/details?pn=US05340603__

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Optically active compound Inventor(s): Mochizuki; Nobuo (Odawara, JP), Uchida; Seiichi (Oiso-machi, JP), Umeda; Nobuhiro (Odawara, JP) Assignee(s): Nippon Soda Co., Ltd. (Tokyo, JP) Patent Number: 5,856,480 Date filed: May 1, 1997 Abstract: The present invention is directed to (R)-(-)-4,5-dihydro-5-methyl-6-›4-›(2propyl-3-oxo-1-cyclohexenyl)amino!ph enyl!-3(2H)-pyridazinone, the crystalline form

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thereof and a method for manufacturing the said compound and the said crystalline form.The compound of the present invention has excellent inhibitory effect on platelet aggregation while giving less side effect, and therefore, it is useful to utilize the compound as an antithrombotic drug. In addition, the compound of the present invention has bronchodialatic effect as well, and it is therefore useful to utilize the compound for chemotherapy of chronic obstructive lung disease, such as asthma and bronchitis.Moreover, the compound of the present invention is useful for chemotherapy of the diseases relating to the concentration of cAMP in cells, such as hypertension, ulcer, diabetes mellitus and cancer.Again, crystalline form of the said compound is the most suitable form in order to supply stable and homogeneous bulk thereof. Excerpt(s): The present invention relates to optically active pyridazinone derivative effectual as an inhibitory agent of platelet aggregation and methods for manufacturing the said pyridazinone derivative. It is well known in the art that pyridazinone compounds have an inhibitory effect on platelet aggregation, and the racemic modifications of the pyridazinone compound of the present invention are disclosed in WO 94/09784 corresponding to U.S. Pat. No. 5,663,172. The said racemic modification has significant inhibitory effect on platelet aggregation, and the side effect caused thereby has been improved to an extent. Web site: http://www.delphion.com/details?pn=US05856480__ •

Percussive aid for the treatment of chronic lung disease Inventor(s): Bryan; William C. (Baldenboro, NC), Colvin; David P. (Apex, NC), Colvin; Virginia S. (Raleigh, NC), Gravely; Benjamin T. (Raleigh, NC), Lord; Charles J. (Cary, NC), Moody; David B. (Cary, NC), Mulligan; James C. (Raleigh, NC), Whitney; Raymond A. (Raleigh, NC) Assignee(s): Triangle Research and Development Corporation (Raleigh, NC) Patent Number: 5,261,394 Date filed: September 30, 1991 Abstract: A percussive aid provides percussive force to aid in the treatment of Cystic Fibrosis and other pulmonary blockage diseases. The device includes a frame with a pair of reciprocating arms mounted thereto at one of their ends. The other end of the arms mount impactor cups. A spring is associated with each of the cups. A drive mechanism is carried by the frame and moves the arms through a predetermined path of travel from a first uncocked position to a second cocked position of maximum deflection wherein the spring is placed in tension when the arm is tripped. Excerpt(s): This invention relates generally to the field of the treatment of chronic lung disease and more particularly, to the field of percussive aids used to loosen purulent secretions from the lungs of persons with chronic respiratory diseases such as cystic fibrosis. Respiratory problems afflict many people throughout the world. Many of these respiratory diseases involve obstruction of the bronchial pathways with bronchial secretions or fluids from the lungs. These diseases may include cystic fibrosis (CF), a much more serious disease. More specifically, with CF patients, the bronchial secretions are very thick and collect in the airways. CF patients require one or more daily percussion treatments to their lung in order to assist in the movement of the aforementioned fluids out of the lungs. As a consequence of reduced oxygen intake and frequent lung infection, CF patients tend to be small, frail and have a life expectancy of less than thirty years. Manual percussion treatments remain the only proven method for

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obtaining lung clearance. According to this method, a parent or other adult normally uses their cupped hands to percuss the patient over all of the lung areas (front, back and sides). Satisfactory percussion of CF patients typically requires at least thirty minutes of treatments twice daily. This procedure is both tiring to caregiver and patient, but it is critical to the patient's health and survival. Disastrous consequences can result when percussion is not administered correctly or with the proper frequency. It will, therefore, be seen that CF patients are often unable to travel or live alone and be independent as a caregiver must be present to administer percussive treatments daily. Web site: http://www.delphion.com/details?pn=US05261394__ •

Sulfonamide compounds, compositions and method of use Inventor(s): Bauer; Barr E. (Elmwood Park, NJ), Czarniecki; Michael F. (Westfield, NJ) Assignee(s): Schering Corporation (Kenilworth, NJ) Patent Number: 4,857,301 Date filed: September 25, 1987 Abstract: Certain substituted sulfonamide quinolines and isoquinolines are disclosed having anti-allergic activity. A preferred use is for the treatment of chronic obstructive lung disease, and in particular, asthma. Excerpt(s): The present invention relates to certain quinoline and isoquinoline sulfonamide compounds, pharmaceutical compositions containing said compounds and methods of using said compounds. European Patent Application No. 851165020.9, published July 16, 1986, and U.S. Pat. No. 4,525,589 disclose related sulfonamides. Also European Patent Application No. 109,023 published on May 23, 1984 and European Patent Application No. 61,673 published on Oct. 6, 1982 similarly disclose related sulfonamides. None of the references discloses substituted sulfonamides for use as antiallergic compounds. R.sup.5 represents H, lower alkyl, --CO.sub.2 R.sup.a, lower alkyl substituted with --CO.sub.2 R.sup.a (where R.sup.a is lower alkyl) or aminoiminomethyl such that when R.sup.5 is H or lower alkyl, f is the integer 1 or 2, and when R.sup.5 is aminoiminomethyl or CO.sub.2 R.sup.a, f is 1. Web site: http://www.delphion.com/details?pn=US04857301__

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System and method for automatically maintaining a blood oxygen saturation level Inventor(s): Mondry; Adolph J. (46340 Concord Dr., Plymouth, MI 48170) Assignee(s): none reported Patent Number: 5,682,877 Date filed: April 15, 1994 Abstract: A system and method for automatically selecting an appropriate oxygen dose to maintain a desired blood oxygen saturation level is disclosed. The system and method are particularly suited for use with ambulatory patients having chronic obstructive lung disease or other patients requiring oxygenation or ventilation. In one embodiment, the method includes delivering a first oxygen dose to the patient while repeatedly sequencing through available sequential oxygen doses at predetermined time intervals until the current blood oxygen saturation level of the patient attains the desired

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blood oxygen saturation level. The method then continues with delivering the selected oxygen dose to the patient so as to maintain the desired blood oxygen saturation level. Excerpt(s): The present invention relates to an oxydosimeter for affecting the blood oxygen saturation SaO.sub.2 in patients using oxygenators and ventilators. Oxygenators and ventilators treat patients who need supplemental oxygenation or who are unable to breathe independently. Recently, a variety of oxygenators and ventilators have been proposed. However, these devices permit significant variation in the blood oxygen saturation level of the patient. The oxygen saturation level SaO.sub.2 of a healthy patient breathing room air exhibits little variation. Significant variation of the oxygen saturation level of a patient may lead to a number of adverse consequences. For example, poor weight maintenance or gain (due to negative nitrogen balance), increased frequency of apnea and poor development in neonates, increased frequency of oxygenation advancement, difficulty in weaning from a ventilator, poor mentation, and decreased survival rates may result. Thus, it is desirable to provide a device which minimizes the variance of the oxygen saturation level SaO.sub.2. Web site: http://www.delphion.com/details?pn=US05682877__ •

Transthoracic intrapulmonary pleuropneumoniae

immunization

against

Actinobacillus

Inventor(s): Rhodes; Marvin B. (Lincoln, NE), Srikumaran; Subramaniam (Lincoln, NE), Stine; Douglas L. (Lincoln, NE) Assignee(s): Board of Regents of the University of Nebraska (Lincoln, NE) Patent Number: 5,456,914 Date filed: January 26, 1993 Abstract: The invention is directed to a method for immunizing an animal for the production of high levels of IgA antibodies against a lung pathogen. The method comprises administering an antigen by transthoracic injection directly into the lung of the animal, the elicited antibodies having specific activity against the administered antigen and lung pathogen of interest. The invention provides a method of stimulating the production of IgA antibodies at mucosal surfaces of the lungs to increase IgA antibody titers in lung fluids and reduce the severity of the lung disease of interest. Excerpt(s): Lung diseases caused by bacterial or viral agents pose a serious problem for farmers and cattle ranchers. One example, porcine pleuropneumoniae in pigs which is caused by the bacterium Actinobacillus pleuropneumoniae, costs pork producers millions of dollars each year. The disease has a complex pathogenesis, and a secreted cytotoxin plays an important role in the production of acute lung lesions. Another example, bovine respiratory disease complex (shipping fever), is a severe fibrinous pneumonia that has had an economic impact on feedlot and stocker cattle. Shipping fever has a complex etiology, with the probable cause of the disease being a combination of environmental stress factors and viral and bacterial infection. To protect animals from lung disease, it is essential to achieve a sufficiently high level of IgA antibodies in the lungs to prevent adherence of invading microorganisms to mucosal surfaces and neutralize potentially damaging virulence factors. Although attempts have been made to develop methods to deliver antigens to the lungs to stimulate antibody production, there are significant drawbacks to existing methods of immunization. Administration of vaccines by intramuscular or subcutaneous injection do not provide sufficiently high levels of IgA antibodies in lung fluids. Intratracheal or intranasal delivery of antigens by

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cannulation or aerosolization are labor-intensive and not practical for routine or largescale application. In addition, the ciliated mucosa of the pulmonary tract functions in a manner that removes foreign antigens, which makes it difficult to deliver a reliable and immunologically effective amount of an antigen to the lungs by such methods. The difficulties in administering antigens to the lungs has contributed to the present lack of efficacious vaccines for the prevention of bacterial and viral-induced infections of the lungs. Therefore, a need exists for an effective, simple method for vaccinating an animal against lung disease. Web site: http://www.delphion.com/details?pn=US05456914__ •

Use of thioredoxin-like molecules for induction of MnSOD to treat oxidative damage Inventor(s): Das; Kumuda C. (Aurora, CO), White; Carl W. (Denver, CO) Assignee(s): National Jewish Medical and Research Center (Denver, CO) Patent Number: 5,985,261 Date filed: June 27, 1997 Abstract: A method to increase cellular MnSOD production in an animal to treat oxidative damage by administering a protein having a thioredoxin active-site in reduced state. A composition and a method to protect an animal from lung disease are provided. Excerpt(s): The present invention generally relates to a method to treat oxidative damage in an animal, in particular, by increasing the cellular level of MnSOD in an animal. One embodiment of the present invention is directed to a method to increase the cellular level of MnSOd in an animal to treat oxidative damage. Such a method comprises administering to an animal an amount of a protein containing a thioredoxin active-site in reduced state which is effective to induce the production of MnSOD in an animal. In a preferred embodiment, a protein of the present invention is administered to an animal by a route selected from the group of nasal, inhaled and intratracheal routes. In another embodiment, such a protein has a preferred half-life in an animal of between about 16 and about 24 hours. In yet another embodiment, a protein containing a thioredoxin active-site in reduced state comprises the amino acid sequence C-G-P-C. Another embodiment of the present invention relates to a composition for increasing the cellular level of MnSOD in an animal to treat oxidative damage. Such a composition comprises a protein containing a thioredoxin active-site in reduced state. Such a protein is formulated in a pharmaceutically acceptable delivery vehicle which provides a halflife of between about 5 minutes and about 24 hours in an animal. Web site: http://www.delphion.com/details?pn=US05985261__

Patent Applications on Lung Disease As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to lung disease:

10

This has been a common practice outside the United States prior to December 2000.

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Anti-inflammatory and psoriasis treatment and protein kinase inhibition by hydroxyltilbenes and novel stilbene derivatives and analogues Inventor(s): Chen, Genhui; (Burnaby, CA), Hu, Kaiji; (Burnaby, CA), Li, Jianxiong; (Port Moody, CA), Webster, John M.; (North Vancouver, CA), Zhu, Jiang; (Burnaby, CA) Correspondence: Pennie & Edmonds; 1155 Avenue OF The Americas; New York; NY; 10036-2711; US Patent Application Number: 20030171429 Date filed: October 28, 2002 Abstract: Disclosed herein are compositions containing hydroxylstilbenes or their derivatives or analogues. The compositions are useful to inhibit protein kinease, and for the treatment of inflammatory diseases, including psoriasis, multiple sclerosis, rhumatoid arthritis, restinosis, inflammatory bowel disease, and inflammatory lung disease. They are also useful to treat surgical adhesions and graft rejection. Novel derivatives and analogues are also disclosed. Excerpt(s): The stilbenes isolated from Photorhabdus species bacteria are known to have antibiotic activity. See V. J. Paul, S. Frautschv, W. Fenical, and K. H. Nealson, Journal of Chemical Ecology, 7: 589-597 (1981), and K. Hu, J. Li, W. Wang, H. Wu, H. Lin and J. M. Webster, Canadian Journal of Microbiology. 44: 1072-1077 (1998). However, these compounds have not been shown to have other biological activity. A similar compound, resveratrol, has been disclosed as having cancer preventive (Jang et al. 1997) and protein kinase C inhibitory (Garcia-Garcia et. al., 1999) activities. There are many common conditions that cannot be treated successfully by antibiotics. Some of these are inflammatory diseases. The compounds of the invention possess specific antiinflammatory properties. Inflammatory diseases, whether of a chronic or acute nature, represent a substantial problem in the healthcare industry. Chronic inflammation is considered to be inflammation of a prolonged duration (weeks or months) in which active inflammation, tissue destruction and attempts at healing are proceeding simultaneously (Robbins Pathological Basis of Disease by R. S. Cotran, v. Kumar, and S. L. Robbins, W. B, Saunders Co., p. 75, 1989). Although chronic inflammation can follow an acute inflammatory episode, it can also begin as an insidious process that progresses with time, for example, as a result of a persistent infection (e.g., tuberculosis, syphilis, fungal infection) which causes a delayed hypersensitivity reaction, prolonged exposure to endogenous (e.g., elevated plasma lipids) or exogenous (e.g., silica, asbestos, cigarette tar, surgical sutures) toxins, or, autoimmune reactions against the body's own tissues (e.g., rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, psoriasis). Chronic inflammatory diseases therefore, include many common medical conditions such as rheumatoid arthritis, restenosis, psoriasis, multiple sclerosis, surgical adhesions, tuberculosis, and chronic inflammatory lung and airway diseases (e.g., asthma, pneumoconiosis, chronic obstructive pulmonary disease, nasal polyps and pulmonary fibrosis). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Composition, formulations & kit for treatment of respiratory & lung disease with dehydroepiandrosterone(s) steroid & an anti-muscarinic agent(s) Inventor(s): Nyce, Jonathan W.; (Titusville, NJ), Robinson, Cynthia B.; (Wayne, PA) Correspondence: Howrey Simon Arnold & White, Llp; Box 34; 301 Ravenswood AVE.; Menlo Park; CA; 94025; US Patent Application Number: 20030216329 Date filed: June 12, 2003 Abstract: A pharmaceutical or veterinary composition comprises a non-corticosteroids, and/or salts thereof, and an anti-muscarinic (anti-cholinergic) agent, and.backslash.or pharmaceutically or veterinarilly acceptable salts thereof. The composition is provided in various formulations and in the form of a kit. The products of this patent are useful in the prophylaxis and treatment of various respiratory, lung and malignant diseases. Excerpt(s): This application is a continuation-in-part of PCT Application No. PCT/US02/12552 (EPI-10449), entitled COMPOSITION, FORMULATIONS & KIT FOR TREATMENT OF RESPIRATORY & LUNG DISEASE WITH NONGLUCOCORTICOID STEROIDS &/OR UBIQUINONE & BRONCHODILATING AGENT, filed Apr. 22, 2002, which is based on US Provisional Application 60.backslash.286,139, filed Apr. 24, 2001, by Jonathan W. Nyce. This invention relates to a composition and formulations comprising a dehydroepiandrosterone(s) of chemical formula (I), (II), (III), (IV) and (V), and/or salts thereof, and an anti-muscarinic receptor agent(s), and/or salts thereof, and optionally other bioactive agents and formulation components. These products are useful in the treatment of respiratory and lung diseases in general and in the treatment of conditions such as COPD, asthma, allergic rhinitis, and the like. Respiratory ailments are extremely common in the general population, and more so in certain ethnic groups, such as African Americans. In some cases they are accompanied by inflammation, which aggravates the condition of the lungs. Diseases such as Chronic obstructive pulmonary disease (COPD), asthma, allergic rhinitis, and Acute Respiratory Distress Syndrome (ARDS), including RDS in pregnant mothers and in premature born infants, among others, are common diseases in industrialized countries, and in the United States alone, they account for extremely high health care costs. These diseases have recently been increasing at an alarming rate, both in terms of prevalence, morbidity and mortality. In spite of this, their underlying causes still remain poorly understood. COPD is characterized by airflow obstruction that is generally caused by chronic bronchitis, emphysema, or both. Emphysema is characterized by abnormal permanent enlargement of the air spaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis. Chronic bronchitis is characterized by chronic cough, mucus production, or both, for at least three months for at least two successive years where other causes of chronic cough have been excluded. COPD characteristically affects middle aged and elderly people, and is one of the leading causes of morbidity and mortality worldwide. In the United States it affects about 14 million people and is the fourth leading cause of death, and both morbidity and mortality, have risen, for example, in the United States by 41% since 1982, and the age-adjusted death rates by 71% between 1966 and 1985. This contrasts with a decline over the same period in age-adjusted mortality from all causes (22%), and from cardiovascular diseases (45%). COPD, however, is preventable, given that its main cause is thought to be exposure to cigarette smoke. The disease is rare in lifetime non-smokers. Other proposed etiological factors include airway hyperresponsiveness or hypersensitivity, ambient air pollution, and allergy. The airflow obstruction in COPD is usually progressive in people who continue to smoke, and

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results in early disability and shortened survival time. Stopping smoking reverts the decline in lung function to values for non-smokers. Many COPD patients will use medication chronically for the rest of their lives, and will need increased doses and additional drugs during exacerbations. Amongst the currently available treatments for COPD, short-term benefits, but not long term effects, were found on its progression, from administration of anti-cholinergic drugs,.beta.2 adrenergic agonists, and oral steroids. Neither anti-cholinergic drugs nor.beta.2 adrenergic agonists have an effect on all people with COPD; nor do the two agents combined. The adverse effects of theophyllines and the need for frequent monitoring limit their usefulness. There is no evidence that anti-cholinergic agents affect the decline in lung function, and mucolytics have been shown to reduce the frequency of exacerbations but with a possible deleterious effect on lung function. The long-term effects of.beta.2 adrenergic agonists, oral corticosteroids, and antibiotics have not yet been evaluated, and up to the present time no other drug has been shown to affect the progression of the disease or survival. Thus, there is very little currently available to alleviate symptoms of COPD, prevent exacerbations, preserve optimal lung function, and improve daily living activities an quality of life. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for treating emphysema Inventor(s): Ingenito, Edward; (Kingston, MA) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030181356 Date filed: March 11, 2003 Abstract: The present invention features compositions and methods for treating emphysema by reducing the amount of force the fibers in the lung (e.g., the collagen and elastin fibers in the walls of the alveoli) must bear. More particularly, in one embodiment, the invention features a pharmaceutically acceptable composition comprising a lipid that, when applied to an enlarged alveolus (e.g., an alveolus having a diameter substantially larger than (e.g., 5, 10, 20, 50, or 100% or more than) the average alveoli in a healthy patient (i.e., a patient with no discernable lung disease), exerts a surface tension within the alveolus that substantially reduces the stress on fibers within the alveolus when inflated by a normal inspiration. The composition can display a.gamma.* of about 30 to about 70 dynes/cm. Excerpt(s): This application claims the benefit of the filing date of U.S. Ser. No. 60/363,118, which was filed on Mar. 11, 2002. The contents of the prior provisional application is hereby incorporated by reference in its entirety. This invention features compositions and methods for treating patients who have certain lung diseases, such as emphysema. Emphysema, together with asthma and chronic bronchitis, represent a disease complex known as chronic obstructive pulmonary disease (COPD). These three diseases are related in that they each cause difficulty breathing and, in most instances, they progress over time. There are substantial differences, however, in their etiology, pathology, and prognosis. For example, while asthma and chronic bronchitis are diseases of the airways, emphysema is associated with irreversible, destructive changes in lung parenchyma distal to the terminal bronchioles. Cigarette smoking is the primary cause of emphysema; the smoke triggers an inflammatory response within the lung, which is associated with an activation of both elastase and matrix metallo-proteinases (MMPs). These enzymes degrade key proteins that make up the tissue network of the

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lungs (Shapiro et al., Am. J. Resp. Crit. Care Med. 160:s29-s32, 1999; Hautamaki et al., Science 277:2002-2004). In fact, the pathological determinant of lung dysfunction in emphysema seems to be the progressive destruction of elastic tissue, which causes loss of lung recoil and progressive hyper-expansion. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Devices for creating collateral channels in the lungs Inventor(s): Laufer, Michael D.; (Menlo Park, CA), Roschak, Ed; (Mountain View, CA), Tanaka, Don; (Saratoga, CA) Correspondence: Morrison & Foerster Llp; 755 Page Mill RD; Palo Alto; CA; 94304-1018; US Patent Application Number: 20020049370 Date filed: July 18, 2001 Abstract: The devices and methods disclosed herein are directed to altering gaseous flow within a lung to improve the expiration cycle of, for instance, an individual having Chronic Obstructive Pulmonary Disease. More particularly, these devices and methods produce and to maintain collateral openings or channels through the airway wall so that expired air is able to pass directly out of the lung tissue to facilitate both the exchange of oxygen ultimately into the blood and/or to decompress hyper-inflated lungs. The devices and methods also disclose locating and selecting a site for creation of a collateral opening.The invention is directed to methods and devices to altering gaseous flow within a lung to improve the expiration cycle of an individual, particularly individuals having Chronic Obstructive Pulmonary Disease (COPD). More particularly, methods and devices are disclosed to produce and to maintain collateral openings or channels th rough the airway wall so that expired air is able to pass directly out of the lung tissue to facilitate both the exchange of oxygen ultimately into the blood and/or to decompress hyper-inflated lungs.The term "Chronic Obstructive Pulmonary Disease" (COPD) is generally used to describe the disorders of emphysema and chronic bronchitis. Previously, COPD was also known as Chronic Obstructive Lung Disease (COLD), Chronic Airflow Obstruction (CAO), or Chronic Airflow Limitation (CAL). Some also consider certain types of asthma to fall under the definition of COPD. Emphysema is characterized by an enlargement of air spaces inside the lung. Hence, Emphysema is an anatomic definition and it can only be presumed in a living patient. Chronic bronchitis is characterized by excessive mucus production in the bronchial tree. Chronic bronchitis is a clinical definition and denotes those individuals who meet criteria defining the disease. It is not uncommon for an individual to suffer from both disorders. Excerpt(s): In 1995, the American Lung Association (ALA) estimated that between 15-16 million Americans suffered from COPD. The ALA estimated that COPD was the fourthranking cause of death in the U.S. The ALA estimates that the rates of emphysema is 7.6 per thousand population, and the rate for chronic bronchitis is 55.7 per thousand population. Those inflicted with COPD face disabilities due to the limited pulmonary functions. Usually, individuals afflicted by COPD also face loss in muscle strength and an inability to perform common daily activities. Often, those patients desiring treatment for COPD seek a physician at a point where the disease is advanced. Since the damage to the lungs is irreversible, there is little hope of recovery. Most times, the physician cannot reverse the effects of the disease but can only offer treatment and advice to halt the progression of the disease. To understand the detrimental effects of COPD, the workings of the lungs requires a cursory discussion. The primary function of the lungs

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is to permit the exchange of two gasses by removing carbon dioxide from venous blood and replacing it with oxygen. Thus, to facilitate this exchange, the lungs provide a blood gas interface. The oxygen and carbon dioxide move between the gas (air) and blood by diffusion. This diffusion is possible since the blood is delivered to one side of the bloodgas interface via small blood vessels (capillaries). The capillaries are wrapped around numerous air sacs called alveoli which function as the blood-gas interface. A typical human lung contains about 300 million alveoli. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Dinucleotides useful for the treatment of lung disease Inventor(s): Boucher, Richard C. JR.; (Chapel Hill, NC), Geary, Cara A.; (Seattle, WA), Lazarowski, Eduardo R.; (Durham, NC), Stutts, Monroe Jackson III; (Chapel Hill, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20010041682 Date filed: May 7, 2001 Abstract: A pharmaceutical formulation comprises, in an amount effective to hydrate lung mucous secretions, a compound of Formula (I): 1whereinn is from 1 to 6;X is --OH or --SH;A and B are each independently selected from the group consisting of: 2 wherein R is H or Br;or a pharmaceutically acceptable salt thereof, in a pharmaceutically acceptable carrier. A method of hydrating mucous secretions in the lungs of a subject in need of such treatment, comprising administering to the lungs of the subject a compound of Formula I as given above, is also disclosed. Excerpt(s): This application is a continuation-in-part of commonly owned, co-pending U.S. patent application Ser. No. 08/486,988, filed Jun. 7, 1995, the disclosure of which is incorporated by reference herein in its entirety. This invention relates to certain dinucleotides, pharmaceutical formulations containing the same, and methods of hydrating retained mucous secretions in the lungs of a subject by administering dinucleotides to the subject. In cystic fibrosis several functions of airway epithelia are abnormal, and deficiencies in both Cl.sup.- transport and Na.sup.+ absorption are well documented. See, e.g. Knowles et al., Science 221, 1067 (1983); Knowles et al., J. Clin. Invest. 71, 1410 (1983). Regulation of ion transport might have potential therapeutic benefit in lung diseases characterized by abnormalities in epithelial ion transport, e.g., cystic fibrosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method and measuring equipment for measuring nitric oxide concentration in exhaled air Inventor(s): Lehtimaki, Lauri; (Tampere, FI), Moilanen, Eeva; (Tampere, FI) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20020193698 Date filed: May 15, 2002 Abstract: A method for measuring nitric oxide concentration in exhaled air through a blow tube of a measuring equipment. The nitric oxide concentration is measured in the

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exhaled air flowing in the blow tube, a flow rate of the exhaled air flowing through the blow tube is measured during the exhalation and flow resistance of the blow tube is adjusted on the basis of the measured flow rate value such that the flow rate of the exhaled air substantially remains at a preset value. The method is used to diagnose an inflammatory lung disease in a patient whereby an increased nitric oxide concentration indicates an inflammatory lung disease, such as alveolitis. Excerpt(s): The invention relates to a method for measuring nitric oxide (NO) concentration in exhaled air, in which method the exhaled air is blown through a blow tube in measuring equipment, and nitric oxide concentration is measured in the exhaled air flowing in the blow tube. Further, the invention relates to measuring equipment for measuring the nitric oxide concentration of exhaled air, the measuring equipment comprising a blow tube, through which the exhaled air is blown and a measuring means for measuring the nitric oxide concentration of the exhaled air flowing through the blow tube. Nitric oxide is a gaseous molecule that is intrinsically easily reactive. It also acts in the body as a signaling molecule that has various physiological and pathophysiological functions. For instance, nitric oxide regulates the function of respiratory organs in various conditions both in normal physiological and inflammatory states. Even though nitric oxide is easily reactive, some of the nitric oxide produced in the lungs mixes with pulmonary air and minor amounts of nitric oxide can be measured in exhaled air. In inflammatory lung diseases, such as asthma and alveolitis, the nitric oxide concentration of the exhaled air is higher than normal, since the nitric oxide concentration has increased because of the inflammation. So, the nitric oxide concentration can be used as an indicator of an inflammation in the lungs and of inflammatory diseases. The nitric oxide concentration of exhaled air can be measured by an analyzer intended for that purpose. Currently, analyzers based on ozone chemiluminescence technology are commercially available on the market. In known measuring methods, a person to be examined exhales the exhalation air into an analyzer such that the flow rate of the exhaled air remains substantially constant. By this measuring method it is possible to detect a rise in the nitric oxide concentration of the exhaled air and thus to conclude, on the basis of the increased nitric oxide concentration, that there is inflammation in the lungs, but in which part of the lungs said inflammation is located cannot be found out by this method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and system for lung disease detection Inventor(s): Avila, Ricardo Scott; (Clifton Park, NY), Hastings, Shannon Lee; (Clifton Park, NY), Kaucic, Robert August JR.; (Niskayuna, NY), Lorensen, William Edward; (Ballston Lake, NY), McCulloch, Colin Craig; (Charlton, NY), Mundy, Joseph Leagrand; (Schenectady, NY), Turek, Matthew William; (Glenville, NY) Correspondence: General Electric Company; Global Research Center; Patent Docket RM. 4a59; PO Box 8, BLDG. K-1 Ross; Niskayuna; NY; 12309; US Patent Application Number: 20030095692 Date filed: November 20, 2001 Abstract: A method for processing medical images for use in the detection and diagnosis of disease comprises classifying regions of interest within the medical images based on a hierarchy of anatomical models and signal models of signal information of an image acquisition device used to acquire the medical images. The anatomical models are derived to be representative of anatomical information indicative of a given disease. A

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computer-aided system for use in the diagnosis and detection of disease comprises an image acquisition device for acquiring a plurality of image data sets and a processor adapted to process the image data sets. The processor is adapted to classify selected tissue types within the image data sets based on a hierarchy of signal and anatomical models and the processor is further adapted to differentiate anatomical context of the classified tissue types for use in the diagnosis and detection of disease. Excerpt(s): This invention relates to a method and system for processing medical image data to aid in the detection and diagnosis of disease, and more particularly, to a method and system for detecting lung disease in medical images obtained from a x-ray computed tomography (CT) system. A x-ray chest radiograph system is the more commonly used diagnostic tool useful for the purpose of detecting lung disease in humans. Lung disease such as bronchitis, emphesema and lung cancer are also detectable in chest radiographs and CT. However, CT systems generally provide over 80 separate images for a single CT scan thereby providing a considerable amount of information to a radiologist for use in interpreting the images and detecting suspect regions that may indicate disease. Suspect regions are defined as those regions a trained radiologist would recommend following through subsequent diagnostic imaging, biopsy, functional lung testing, or other methods. The considerable volume of data presented by a single CT scan presents a time-consuming process for radiologists. Conventional lung cancer screening generally involves a manual interpretation of the 80 or more images by the radiologist. Fatigue is therefore a significant factor affecting sensitivity and specificity of the human reading. In other diseases, such as emphysema, it is difficult for a radiologist to classify the extent of disease progression by only looking at the CT images. Quantitative analysis of the anatomy is required. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for detecting bacterial exacerbations of chronic lung disease Inventor(s): Murphy, Timothy F.; (East Amherst, NY), Sethi, Sanjay; (East Amherst, NY) Correspondence: Ranjana Kadle; Hodgson Russ Llp; Suite 2000; One M&t Plaza; Buffalo; NY; 14203-2391; US Patent Application Number: 20020001820 Date filed: February 9, 2001 Abstract: The present invention provides a method for distinguishing bacterial from non-bacterial exacerbations of chronic lung disease. The method comprises detecting the presence of elastase in patient sputum containing secretions of the lower respiratory tract. Excerpt(s): This application claims the priority of U.S. provisional application serial no. 60/181,620 filed on Feb. 10, 2000, the disclosure of which is incorporated herein by reference. The present invention relates generally to the area of lower respiratory tract infections. More particularly, the present invention provides a method for differentiating bacterial versus non-bacterial exacerbations of chronic lung disease. Chronic bronchitis and other lung diseases including cystic fibrosis and bronchiectasis, are associated with intermittent exacerbations (such as acute exacerbations of chronic bronchitis (AECB)) that lead to worsening of the chronic symptoms of productive cough and dyspnea. These exacerbations cause considerable morbidity, and in patients with concomitant airway obstruction such as chronic obstructive pulmonary disease (COPD), are a major cause of mortality (Burrows et al., 1969, N. Engl. J. Med., 280:397-404). AECB

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can have one or more of several different etiologies (Sethi, 1998, Infect. Dis. Clin. Pract., 7:S300-S308). Virus infection, identified by a four-fold rise in antibody titer or by viral isolation, causes a third of exacerbations (Gump et al., 1976, Am. Rev. Respir. Dis., 113:465-473; Buscho et al., 1978, J. Infect. Dis., 137:377-383; Smith et al., 1980, Am. Rev. Respir. Dis., 121:225-232). Serological evidence of atypical bacterial infection, mostly by Chlamydia pneumoniae, is seen in 5-10% of exacerbations (Blasi et al., 1993, Eur. Respir. J., 6:19-22; Miyashita et al., 1998, Chest, 114:969-971). Bacterial pathogens, especially nontypeable Haemophilus influenzae, Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis and Pseudomonas aeruginosa are isolated from sputum in about 50% of exacerbations (Sethi, 1998, supra). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for treating allergic lung disease Inventor(s): Carson, Dennis A.; (Del Mar, CA), Raz, Eyal; (Del Mar, CA) Correspondence: Bozicevic, Field & Francis Llp; 200 Middlefield RD; Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20030027782 Date filed: May 13, 2002 Abstract: The invention is directed to a method for treating both the early and late phases of allergic asthma by introducing naked polynucleotides which operatively encode for the asthma-initiating antigen into the host. The antigen-encoding polynucleotides are administered to host tissues which contain a high concentration of antigen presenting cells (e.g., skin and mucosa) relative to other host tissues. Expression of the asthma-initiating antigen encoding polynucleotides of the invention inside of antigen presenting cells (without substantial secretion therefrom) induces antigen tolerance while suppressing IgE antibody formation in the early phase of the disease, and also suppresses cytokine-mediated eosinophil accumulation in the late phase of the disease. Devices and compositions for use in the methods of the invention are also described. Excerpt(s): This is a continuation-in-part of U.S. patent application Ser. No. 08/333,068, filed Nov. 1, 1994, which is in turn a continuation-in-part of U.S. patent application Ser. No. 08/112,440, filed in the United States Patent and Trademark Office on Aug. 26, 1993. The invention relates to a method for treating both the early and late phases of allergic lung disease. In particular, the invention relates to a method for immunizing a host against allergic asthma through use of asthma-initiating antigen-encoding polynucleotide compositions. Asthma is one of the common chronic lung diseases of industrialized countries. The airway narrowing which characterizes the disease is associated with antigen stimulated immune system activation, including elevation of antigen-specific IgE levels in the early phase of the disease and eosinophil infiltration of lung tissue in the late phase of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of promoting mucosal hydration with certain uridine, adenine and cytidine diphosphates and analogs thereof Inventor(s): Jones, Arthur C.; (Durham, NC), Rideout, Janet L.; (Raleigh, NC), Yerxa, Benjamin R.; (Raleigh, NC) Correspondence: Howrey Simon Arnold & White, Llp; Box 34; 301 Ravenswood AVE.; Menlo Park; CA; 94025; US Patent Application Number: 20020052338 Date filed: December 3, 2001 Abstract: A method and preparation for the stimulation of mucosal hydration in a subject in need of such treatment is disclosed. The method comprises administering to the mucosal surfaces of the subject a purinergic receptor agonist such as uridine 5'diphosphate (UDP), dinucleotide triphosphates; cytidine 5'-diphosphate (CDP), adenosine 5'-diphosphate (ADP), or their therapeutically useful analogs and derivatives, in an amount effective to stimulate mucin secretion. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include: topical administration via a liquid, gel, cream, or as part of a contact lens or selective release membrane; or systemic administration via nasal drops or spray, inhalation by nebulizer or other device, oral form (liquid or pill), injectable, intraoperative instillation or suppository form. A method for facilitating the expectoration of sputum for the purpose of detecting cellular abnormalities indicative of lung disease is also disclosed. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/512,867, filed Feb. 25, 2000; which claims the benefit of U.S. Provisional Application No. 60/121,754, filed Feb. 26, 1999. This invention relates to a method of regulating secretions in and around the mucous membranes of a mammal by administering purinergic receptor agonists such as certain uridine, adenine, or cytidine diphosphates as well as other nucleoside phosphate compounds. There are many situations where it is therapeutically desirable to increase the amount of hydration on mucosal surfaces of the body. Mucus membranes are hydrated surface epithelial tissues that line cavities exposed to the outside environment. These mucosal surfaces of the body must stay hydrated with the proper mixtures of water, salt, mucin and other proteins in order to defend the body from the outside world and remain comfortable. The mucus membranes play a major role in fighting off infections and keeping the exposed organs clean and healthy. Mucus membranes are found on the surface of the eye, vagina, sinonasal cavities and mouth (oropharyngeal). Impaired hydration of these mucus membranes leads to medical conditions such as: dry eye, vaginal dryness, rhinosinusitis, dry mouth, corneal injury, and others. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compositions for the treatment and prevention of lung disease Inventor(s): Chandraratna, Roshantha A.; (Laguna Hills, CA), Massaro, Donald; (Washington, DC), Massaro, Gloria DeCarlo; (Washington, DC) Correspondence: Carlos A. Fisher; Allergan, INC.; 2525 Dupont Drive; Irvine; CA; 92623; US Patent Application Number: 20010053758 Date filed: July 31, 2001

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Abstract: Methods and compositions for the treatment of lung disease, such as emphysema and/or bronchopulmonary dysplasia, in a mammal. Also disclosed are methods promoting the formation of alveolar septa and increasing the gas-exchange surface area of a mammalian lung, and for the prevention and/or treatment of alveolar destruction. Excerpt(s): This invention concerns the use of retinoic acid receptor (RAR) antagonists for the inhibition of alveolar destruction and/or to promote the formation of alveoli in mammalian lung tissue deficient in adequate numbers of functional alveoli. Among aerobic animals, the lung functions to provide an interface for the exchange of gases between blood and the atmosphere. The agents of this exchange are numerous small sacs termed alveoli (in adult humans about 300,000,000 per lung) that provide a gas permeable-liquid impermeable barrier between the gas and liquid phases. Between the alveoli are numerous capillaries carrying deoxygenated blood to the lung from the tissues and oxygenated blood from the alveoli to the tissues. The partial pressure of oxygen in the lungs is approximately 100 mm Hg at sea level; at this pressure the binding of oxygen by hemoglobin in the erythrocytes is favored. The alveoli thus provide a means for presenting the oxygen to hemoglobin to permit the conversion of deoxyhemoglobin to hemoglobin. Because the exchange occurs at the surface of the gas/blood barrier, alveoli have evolved as a means for providing extremely high surface area in a compact overall area, thus maximizing possible gas exchange. Lack of adequate gas exchange would lead to disability which could progress to death. Diseases that result in fewer alveoli therefore are quite serious, and are common causes of inadequate oxygenation and resultant disability and death. Among such diseases are brochopulmonary dysplasia (BPD) and emphysema. BPD is a disease of prematurely born infants, and is characterized mainly by a failure of the infant to form a sufficient number of appropriately-sized alveoli. Emphysema, a disease of middle and advanced age, appears to be due to progressive proteinase-induced alveolar destruction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and devices for use in performing pulmonary procedures Inventor(s): Deem, Mark E.; (Mountain View, CA), French, Ronald; (San Jose, CA), Gifford, Hanson S. III; (Woodside, CA), Sutton, Douglas; (Pacifica, CA) Correspondence: Stephanie L. Seidman; Heller Ehrman White & Mcauliffe Llp; 7th Floor; 4350 LA Jolla Village Drive; San Diego; CA; 92122-1246; US Patent Application Number: 20030192550 Date filed: April 18, 2003 Abstract: Systems, methods and devices for performing pulmonary procedures, and in particular treating lung disease. A flow control element includes a valve that prevents airflow in the inhalation direction but permits airflow in the exhalation direction. The flow control element is guided to and positioned at the site by a bronchoscope that is introduced into the patient's trachea and used to view the lungs during delivery of the flow control element. The valve may include one, two or more valve elements, and it may be collapsible for easier delivery. A source of vacuum or suction may be used to increase the amount of fluid withdrawn from the lung tissue. A device for measuring hollow structures, such as bronchioles, and a device for removing a previously-placed flow control element are disclosed as well.

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Excerpt(s): This application is a continuation of co-pending U.S. patent application Ser. No. 09/519,735 filed Mar. 4, 2000 entitled "Methods and Devices for use in Performing Pulmonary Procedures" by Deem et al., the full disclosure of which is incorporated herein by reference. The present invention relates generally to methods and devices for use in performing pulmonary procedures, and more particularly, procedures for treating various diseases of the lungs. Pulmonary diseases such as emphysema and chronic obstructive pulmonary disease (COPD) reduce the ability of one or both lungs to fully expel air during the exhalation phase of the breathing cycle. The diseased lung tissue is less elastic than healthy lung tissue, which is one factor that prevents full exhalation of air. During breathing, the diseased portion of the lung does not fully recoil due to the tissue being less elastic. Consequently, the diseased (e.g., emphysematic) lung tissue exerts a relatively low driving force, which results in the diseased lung expelling less air volume than a healthy lung. The reduced air volume exerts less force on the airway which allows the airway to close before all air has been expelled, another factor that prevents full exhalation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel Proteins and nucleic acids encoding the same Inventor(s): Burgess, Catherine; (Wethersfield, CT), Mezes, Peter; (Old Lyme, CT), Prayaga, Sudhirdas K.; (O'Fallon, MO), Rastelli, Luca; (Guilford, CT), Shimkets, Richard A.; (West Haven, CT), Zerhusen, Bryan; (Branford, CT) Correspondence: Ivor R. Elrifi, PH.D.; Mintz, Levin, Cohn, Ferris,; Glovsky And Popeo, P.C.; One Financial Center; Boston; MA; 02111; US Patent Application Number: 20020068279 Date filed: December 5, 2000 Abstract: The invention provides novel human transmembrane (NOVTRAN), neuromedin (NOVNEUR), gonadtropin (NOVGON), and interleukin-1 receptor antagonist (NOVINTRA A and B) proteins (NOVX proteins) and isolated nucleic acid molecules encoding the same. Also provided are antibodies that immunospecifically bind to NOVX polypeptides or polynucleotides, or derivatives, variants, mutants, or fragments thereof. The invention additionally provides methods in which a NOVX polypeptide, polynucleotide, and antibody are used in the detection, prevention, and treatment of a broad range of pathological states. Also provided are methods of diagnosing and treating a lung disease associated with differential expression of human interleukin-1 epsilon. Excerpt(s): This application claims priority to U.S. Ser. No. 60/169,056, filed Dec. 6, 1999; U.S. Ser. No. 60/169,886, filed Dec. 9, 1999; U.S. Ser. No. 60/169,866, filed Dec. 9, 1999; U.S. Ser. No. 60/170,252, filed Dec. 10, 1999; and U.S. Ser. No. 60/175,740, filed January 12, 2000; the teachings of which are incorporated by reference in their entirety. The invention relates to polynucleotides and the polypeptides encoded thereby. Transmembrane proteins, as a class, have been implicated in signal transduction, control of cell adhesion, regulation of cell growth and proliferation (including development and oncogenesis), transport of ions or metabolites (e.g., ion channels), and motility (including the ability to suppress metastatic potential). Expression of many transmembrane proteins has been shown to be associated with a variety of tumors. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Respiratory analysis with capnography Inventor(s): Hampton, David R.; (Woodinville, WA), Krauss, Baruch S.; (Brookline, MA) Correspondence: Shumaker & Sieffert, P. A.; 8425 Seasons Parkway; Suite 105; ST. Paul; MN; 55125; US Patent Application Number: 20030073919 Date filed: October 15, 2001 Abstract: The invention presents techniques for identifying and guiding treatment for medical conditions, based upon the carbon dioxide concentration in the patient's breath. In an exemplary application, the techniques of the invention may be used to distinguish obstructive lung disease from restrictive lung disease, even though the symptoms of the conditions are similar. The techniques of the invention may further be used to monitor the effectiveness of the treatment. Excerpt(s): The invention relates to medical devices, and in particular, to medical devices used to guide diagnosis, monitoring and/or treatment of respiratory conditions. Every day, patients with difficulty breathing seek medical help. In such cases, the patients may complain of shortness of breath, but may have no idea as to the cause of the condition. Many cases of shortness of breath fall into two general categories of respiratory disorders. One category of respiratory disorder that may cause shortness of breath is obstructive lung disease. A patient with obstructive lung disease suffers from a narrowing of the airways leading to the alveoli in the lungs. This narrowing, often caused by inflammatory reactions, results in a reduction of the patient's ability to ventilate the alveoli, because the narrowed airways reduce the maximum velocity of flow through the airways. Chronic obstructive pulmonary diseases such as asthma, bronchitis and emphysema, are some of the disorders that can cause narrowing of the airway. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Single nucleotide polymorphisms associated with interstitial lung disease Inventor(s): Cole, F. Sessions; (St. Louis, MO), Hamvas, Aaron; (St. Louis, MO), Nogee, Lawrence M.; (Towson, MD), Whitsett, Jeffrey A.; (Cincinnati, OH) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20020197646 Date filed: February 14, 2002 Abstract: Single nucleotide polymorphisms (SNPs) in the gene encoding surfactant protein C can be used to diagnose interstitial lung disease and to determine whether an individual is predisposed to developing interstitial lung disease. Single-stranded polynucleotides comprising a contiguous series of nucleotides from a mutant allele of a surfactant protein C gene, as well as antibodies which specifically bind to altered forms of surfactant protein C but not to wild-type surfactant protein C, can be used in various methods to detect the presence of disease-associated SNPs. Excerpt(s): This application claims priority to and incorporates by reference co-pending provisional applications Serial No. 60/268,650 filed Feb. 14, 2001 and Serial No. 60/268,991 filed Feb. 15, 2001. This invention resulted from research funded in whole or in part by National Institutes of Health Grant Nos. HL54703 and HL54187. The Federal

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Government has certain rights in this invention. The invention relates to single nucleotide polymorphisms that are associated with interstitial lung diseases and/or pulmonary fibrosis or with predisposition to these diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System and method for assisting in diagnosis, therapy and/or monitoring of a functional lung disease Inventor(s): Reinstadtler, Juergen; (Hoechberg, DE), Schau, Brigitte; (Rosdorf, DE), Schuelke, Hans-Joachim; (Mainstockheim, DE) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030013946 Date filed: June 17, 2002 Abstract: A computer-implemented method of assisting in diagnosis, therapy, follow-up and/or monitoring of a functional lung disease comprises entering patient demographic data, determining predicted lung function parameters from these demographic data, obtaining lung function measurement data from a spriometry measurement of the patient's lung function, and determining a diagnosis proposal dependent on the demographic data, the predicted and the measured lung function parameters of the patient. The present invention gives a physician, a health manager or the patient himself/herself assistance in the correct diagnosis of a functional lung disease and checking or evaluating an earlier diagnosis and treatment strategies based thereon. The invention helps to find suitable treatment strategies for an individual patient and also allows an early detection of a functional lung disease even if the patient does not yet show corresponding symptoms. Excerpt(s): The present invention relates to a computer system, computer-implemented method and computer program assisting a physician, a case manager or the patient himself/herself in diagnosis/therapy/follow-u- p/monitoring functional lung diseases like asthma or chronic obstructive pulmonary disease (COPD). Diagnosis and treatment of pulmonary diseases is based on published medical guidelines like for example of the American Thoracic Society, Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary disease, Am I Respir/Crit Care Med. Vol. 52, pages S77S120, 1995, Siafakas, N.M., Vermeire, P., Pride, N.B., ERS Consensus Statement: Optimal Assessment and Management of Chronic Obstructive Pulmonary Disease (COPD), Eur Respir J, 8, 1398-1420, 1995; National Heart, Lung and Blood Institute, 1995. Global Initiative for Asthma. U.S. Government Printing Office, Washington, DC. Publication No. (NIH) 95-3659. Based on the patient's disease history, patient's symptoms and measurement results like spirometry/lung function measurements using a spirometer the physician makes his/her diagnosis, discusses the same with the patient and enters it into the patient's records. Depending on the diagnosis the physician checks whether or not a medication is appropriate and when the patient is already on a treatment regimen proposes, if necessary, alternative therapies. The success of the therapy is then reviewed during the next visits of the patient. For making his/her diagnosis, the physician has to review the patient records and, if respiratory measurements are carried out and have to be interpreted, he/she frequently has to look up in detail the interpretation of the measurement values in the relevant guidelines as well as the implication of these results with regard to chronic obstructive lung disease. This process is complicated and timeconsuming.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of inhaled retinoids in the treatment of lung diseases Inventor(s): Tong, William P.; (Flushing, NY), Warrell, Raymond P. JR.; (Westfield, NJ) Correspondence: Oppedahl And Larson Llp; P O Box 5068; Dillon; CO; 80435-5068; US Patent Application Number: 20020035152 Date filed: May 11, 2001 Abstract: Administration of retinoids by inhalation is used to overcome the chronic toxicity problems presented by systemic administration and to make retinoid therapy available as an option for the treatment of fibrotic lung disease, emphysema, and the prevention and treatment of epithelial cancers of the respiratory tract, especially those that are associated with tobacco use. Retinoids are administered by inhalation to the respiratory tract of the individual as an air-borne composition with a metered dose aerosol-producing inhaler, in which the retinoid is dissolved in a combination of a pharmaceutically acceptable chlorofluorocarbon propellant and an alkylamine solubilizing agent. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/171,478 filed Dec. 29, 1998, which is a national phase of International Application Ser. No. PCT/US97/05409 which claims the benefit of priority from U.S. Provisional App. Ser. No. 60/016,246 filed Apr. 19, 1996. Unfortunately, while retinoids have been shown to provide beneficial effects in the prevention of at least some types of cancer, the therapeutic regiment requires chronic administration. Under these circumstances, substantial systemic toxicity may result, including hepatic dysfunction, skeletal malformations, mucositis, hyperlipidemia, hypertriglyceridemia (possibly leading to accelerated atherosclerosis and pancreatitis), hypercalcemia, birth defects, and skin, liver and central nervous system toxicity. This toxicity has limited the utility of retinoids as therapeutic agents in the prevention of cancer and in the treatment of lung diseases. Several potential strategies for mitigating the toxicity of retinoids have been considered, including "drug holidays", reductions in dosage, and development of naturally occurring or synthetic ligands that bind specific nuclear retinoid receptors. Lotan, R., FASEB J 10: 1031 (1996). However, none of these strategies has yielded a substantial increase in therapeutic index. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with lung disease, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “lung disease” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on lung disease.

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You can also use this procedure to view pending patent applications concerning lung disease. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON LUNG DISEASE Overview This chapter provides bibliographic book references relating to lung disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lung disease include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “lung disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on lung disease: •

Long Island Life - Line: A Comprehensive Health Care Directory for Long Island Contact: Junior League of Long Island, 1395 Old Northern Blvd, Roslyn, NY, 11576, (516) 484-0485. Summary: This directory offers access to health-care services in Long Island, NY. Organizations are broken into the following categories: Acquired Immunodeficiency Syndrome (AIDS), alcoholism and drug abuse, bereavement, cancer, children, other diseases, handicapped services, heart and lung disease, home health care, hospice, mental health services, multiple service agencies, senior citizen services, visiting nurses, and women's services. The directory also includes information and advice on alcohol and drug abuse, estate planning, financial and legal affairs, funeral arrangement, organ donation, hospital social services, hospice and nursing home selection, living wills, and Social Security benefits.

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African American : American Indian Alaska Native : Asian American : Hispanic : Pacific Islander : Sources of Health Materials Contact: US Department of Health and Human Services, Public Health Service, Office of Minority Health Resource Center, PO Box 37337, Washington, DC, 20013-7337, (800) 444-6472, http://www.omhrc.gov. Summary: This directory provides a listing of health education information sources for minorities. The directory supplies the reader with the names, addresses, and phone numbers for minority health organizations that can provide information concerning specific health topics. It includes resource listings for health topics such as adolescent pregnancy prevention, aging, the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), cancer, child health, cultural awareness, diabetes, digestive diseases, disabilities, exercise, family planning, general health education, heart disease, high blood pressure, kidney disease, lung disease, lupus, mental health, nutrition, organ transplants, osteoporosis, parenting, prenatal care, sickle cell disease, smoking, stress, stroke, substance abuse, violence, weight control, and women's health. The health information provided is tailored for minorities such as: African Americans, Asian Americans, American Indians, Alaskan Natives, Hispanics, and Pacific Islanders.

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Anti-Tuberculosis Drug Resistance in the World : The WHO/IUATLD Global Project on Anti-Tuberculosis Drug Resistance Surveillance Contact: WHO Stop Tuberculosis Strategy and Operations Unit, World Health Organization, Communicable Diseases, Stop Tuberculosis Department, Stop Tuberculosis Strategy and Operations Unit, 20 Avenue Appia CH-1211, Geneva, http://www.who.int/gtb/index.htm. Summary: This monograph provides findings from the First Phase of the World Health Organization's (WHO) and the International Union Against Tuberculosis (TB) and Lung Disease's (IUATLD) Global Project on anti-TB drug resistance surveillance. Data was gathered from 35 countries in five continents. Surveillance or surveys were conducted on approximately 50,000 TB cases sampled from areas representing 20% of the world's population. Findings show that (1) drug resistance was found in all countries surveyed; (2) there were several "hot spots" where multidrug-resistance (MDR) TB prevalence was high and could threaten control programs (i.e., Latvia, Estonia, Russia, the Dominican Republic, Argentina, and the Ivory Coast); (3)there was a strong correlation between both the overall quality of TB control and use of standardized short course chemotherapy and low levels of drug resistance; and (4) the MDR TB level was a useful indicator of national TB program performance.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “lung disease” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “lung disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “lung

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disease” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

2003 Essential Medical Guide to SARS (Severe Acute Respiratory Syndrome) and Atypical Pneumonia, Influenza (Flu), Antiviral Drugs, Respiratory and Lung Diseases, Infection Control, Coronavirus - Authoritative Federal Information from the CDC, FDA, and NIH for Health Care Providers, Physicians, and Patients (Two CDROM Set) by PM Medical Health News (2003); ISBN: 1592482163; http://www.amazon.com/exec/obidos/ASIN/1592482163/icongroupinterna

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21st Century Collection Centers for Disease Control (CDC) Emerging Infectious Diseases (EID) ¿ Guide to SARS (Severe Acute Respiratory Syndrome) and Atypical Pneumonia, Influenza (Flu), Antiviral Drugs, Respiratory and Lung Diseases, Infection Control, Coronavirus ¿ Authoritative Information from the CDC, FDA, WHO, and NIH for Health Care Providers, Physicians, and Patients (Two CD-ROM Set) by PM Medical Health News; ISBN: 1592482317; http://www.amazon.com/exec/obidos/ASIN/1592482317/icongroupinterna

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Air Pollution and Lung Disease in Adults by Philip Witorsch, Samuel V. Spagnolo (Editor); ISBN: 0849301815; http://www.amazon.com/exec/obidos/ASIN/0849301815/icongroupinterna

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Breathing; physiology, environment and lung disease by Arend Bouhuys; ISBN: 0808907581; http://www.amazon.com/exec/obidos/ASIN/0808907581/icongroupinterna

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Chronic airflow obstruction in lung disease by William M. Thurlbeck; ISBN: 0721688594; http://www.amazon.com/exec/obidos/ASIN/0721688594/icongroupinterna

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Chronic Lung Disease in Early Infancy by Richard D. Bland (Editor), Jacqueline J. Coalson (Editor); ISBN: 0824798716; http://www.amazon.com/exec/obidos/ASIN/0824798716/icongroupinterna

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Chronic Obstructive Lung Disease by Norbert F. Voelkel (Editor), et al (2002); ISBN: 1550091336; http://www.amazon.com/exec/obidos/ASIN/1550091336/icongroupinterna

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Chronic Obstructive Lung Disease: Clinical Treatment and Management by Richard E. and Rhodes, Mitchell Brashear; ISBN: 0801607531; http://www.amazon.com/exec/obidos/ASIN/0801607531/icongroupinterna

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Clinical Management and Experimental Models of Surfactant-Related Lung Disease: Proceedings of the 17th International Workshop on Surfactant Replacement, Cagliari, May 24-26, 2002 (Supplement Issue Biology of the Neonate 2002, 1) by G. Bevilacqua (Editor), et al (2002); ISBN: 3805574339; http://www.amazon.com/exec/obidos/ASIN/3805574339/icongroupinterna

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Clinical Physics and Physiology of Chronic Lung Disease Inhalation Therapy by Tysinger; ISBN: 0398027773; http://www.amazon.com/exec/obidos/ASIN/0398027773/icongroupinterna

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Digging Our Own Graves: Coal Miners and the Struggle over Black Lung Disease (Labor and Social Change) by Barbara Ellen Smith; ISBN: 087722451X; http://www.amazon.com/exec/obidos/ASIN/087722451X/icongroupinterna

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Epidemiology of chronic lung diseases in children by Leon Gordis; ISBN: 0801814367; http://www.amazon.com/exec/obidos/ASIN/0801814367/icongroupinterna

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Fetal Origins of Cardiovascular and Lung Disease by D. J. P. Barker (Editor); ISBN: 082470391X; http://www.amazon.com/exec/obidos/ASIN/082470391X/icongroupinterna

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Gene Therapy in Lung Disease by Steven M. Albelda (Editor), James C. Dobbins (2002); ISBN: 0824708202; http://www.amazon.com/exec/obidos/ASIN/0824708202/icongroupinterna

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Good If Not Great Living With Lung Disease (Last of six) by Phil Petersen, B., Sheree Watson (Editor); ISBN: 0962172642; http://www.amazon.com/exec/obidos/ASIN/0962172642/icongroupinterna

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Imaging of Diffuse Lung Disease by David A. Lynch, et al (2000); ISBN: 1550090925; http://www.amazon.com/exec/obidos/ASIN/1550090925/icongroupinterna

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Immunodeficiency in Patients with Chronic Lung Diseases-Approaches to Immunomodulation (Soviet Medical Reviews Series, Section D) by A.A. Borisova, et al (1989); ISBN: 3718649373; http://www.amazon.com/exec/obidos/ASIN/3718649373/icongroupinterna

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Immunology and Management of Interstitial Lung Diseases: A Clinician's Guide by H. Walters, E. H. Walters (Editor) (1995); ISBN: 0412487403; http://www.amazon.com/exec/obidos/ASIN/0412487403/icongroupinterna

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Immunopathology of Lung Disease by Richard L. Kradin (Editor), Bruce W. S. Robinson (1996); ISBN: 0750692820; http://www.amazon.com/exec/obidos/ASIN/0750692820/icongroupinterna

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Interstitial Lung Disease by Marvin I., Md Schwartz, et al (2003); ISBN: 1550091794; http://www.amazon.com/exec/obidos/ASIN/1550091794/icongroupinterna

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Interstitial Lung Disease; ISBN: 1556640447; http://www.amazon.com/exec/obidos/ASIN/1556640447/icongroupinterna

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Interstitial Lung Disease by C.A.C. Pickering; ISBN: 0852004273; http://www.amazon.com/exec/obidos/ASIN/0852004273/icongroupinterna

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Interstitial Lung Diseases in Children by C. Laraya (1988); ISBN: 0849343003; http://www.amazon.com/exec/obidos/ASIN/0849343003/icongroupinterna

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Interstitial Lung Diseases in Children by L.R. Laraya-Cuasay, Walter T. Hughes (Editor) (1988); ISBN: 0849343038; http://www.amazon.com/exec/obidos/ASIN/0849343038/icongroupinterna

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Katzenstein and Askin's Surgical Pathology of Non-Neoplastic Lung Disease by Anna-Luise A. Katzenstein, et al; ISBN: 0721657559; http://www.amazon.com/exec/obidos/ASIN/0721657559/icongroupinterna

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Lung Disease in the Tropics by Om P. Sharma (Editor); ISBN: 0824783980; http://www.amazon.com/exec/obidos/ASIN/0824783980/icongroupinterna

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Lung Disease State of Art 1996 (1997); ISBN: 0787237655; http://www.amazon.com/exec/obidos/ASIN/0787237655/icongroupinterna

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Lung Disease State of the Art 1978 1979 by John F. Murray (1980); ISBN: 0686776100; http://www.amazon.com/exec/obidos/ASIN/0686776100/icongroupinterna

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Lung Disease State of the Art, 1988-1989 (State of the Art Series) by Reuben M. Cherniack (Editor) (1990); ISBN: 0915116081; http://www.amazon.com/exec/obidos/ASIN/0915116081/icongroupinterna

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Lung Disease, State of the Art, 1990-1992 by Robert A. Klocke (Editor); ISBN: 9994895516; http://www.amazon.com/exec/obidos/ASIN/9994895516/icongroupinterna

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Lung Disease: A Self-Management Program (1994); ISBN: 0815195931; http://www.amazon.com/exec/obidos/ASIN/0815195931/icongroupinterna

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Lung Disease: State of Art, 1990-1992 (1993); ISBN: 0915116103; http://www.amazon.com/exec/obidos/ASIN/0915116103/icongroupinterna

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Lung Disease: State of the Art, 1987-1988 by Reuben M. Cherniack (Editor) (1989); ISBN: 0915116073; http://www.amazon.com/exec/obidos/ASIN/0915116073/icongroupinterna

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Lung Diseases of Children an Introduction (1986); ISBN: 0685433331; http://www.amazon.com/exec/obidos/ASIN/0685433331/icongroupinterna

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Lung Diseases of Children an Introduction by Amer Lung Assn (1986); ISBN: 999840973X; http://www.amazon.com/exec/obidos/ASIN/999840973X/icongroupinterna

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Models of Lung Disease: Microscopy and Structural Methods (Lung Biology in Health and Disease, 47) by Joan Gil (Editor); ISBN: 0824780965; http://www.amazon.com/exec/obidos/ASIN/0824780965/icongroupinterna

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Molecular Biology of Lung Disease by Peter J. Barnes, Robert A. Stockley (Editor); ISBN: 0632033444; http://www.amazon.com/exec/obidos/ASIN/0632033444/icongroupinterna

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Muscular exercise in chronic lung disease = L'exercice musculaire dans les maladies pulmonaires chroniques; ISBN: 0080249302; http://www.amazon.com/exec/obidos/ASIN/0080249302/icongroupinterna

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Nitric Oxide in Pulmonary Processes: Role in Physiology and Pathophysiology of Lung Disease by M. G. Belvisi (Editor), J. A. Mitchell (Editor); ISBN: 3764357185; http://www.amazon.com/exec/obidos/ASIN/3764357185/icongroupinterna

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Non-Neoplastic Advanced Lung Disease (Lung Biology in Health and Disease, 176) by Janet R. Maurer (2003); ISBN: 0824740777; http://www.amazon.com/exec/obidos/ASIN/0824740777/icongroupinterna

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Nuclear Medicine and Lung Diseases (1993); ISBN: 2287004157; http://www.amazon.com/exec/obidos/ASIN/2287004157/icongroupinterna

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Nuclear Medicine and Lung Diseases by P. Diot, et al; ISBN: 3540596054; http://www.amazon.com/exec/obidos/ASIN/3540596054/icongroupinterna

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Obstructive Lung Disease by Stephen G. Jenkinson (Editor) (1992); ISBN: 0443088721; http://www.amazon.com/exec/obidos/ASIN/0443088721/icongroupinterna

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Occupational Lung Disease by Beckett (1992); ISBN: 156053091X; http://www.amazon.com/exec/obidos/ASIN/156053091X/icongroupinterna

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Occupational Lung Disease by J. Bernard L. Lee (Editor); ISBN: 0890049009; http://www.amazon.com/exec/obidos/ASIN/0890049009/icongroupinterna

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Occupational Lung Disease (Contemporary Issues in Pulmonary Disease, Vol 2) by J. Bernard L. Gee (Editor); ISBN: 0443082529; http://www.amazon.com/exec/obidos/ASIN/0443082529/icongroupinterna

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Occupational Lung Disease: An International Perspective by Daniel E. Banks (Editor), John E. Parker (Editor); ISBN: 0412736306; http://www.amazon.com/exec/obidos/ASIN/0412736306/icongroupinterna

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Occupational Lung Diseases (1995); ISBN: 072166556X; http://www.amazon.com/exec/obidos/ASIN/072166556X/icongroupinterna

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Occupational Lung Diseases by W. Keith C. Morgan, et al; ISBN: 0721646719; http://www.amazon.com/exec/obidos/ASIN/0721646719/icongroupinterna

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Occupational Lung Diseases: Research Approaches and Methods (Lung Biology in Health and Disease) by H. Weill, M. Turner Warwick (1981); ISBN: 0824713621; http://www.amazon.com/exec/obidos/ASIN/0824713621/icongroupinterna

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Parasitic Lung Diseases by Adel A. F. Mahmoud (Editor); ISBN: 0824797221; http://www.amazon.com/exec/obidos/ASIN/0824797221/icongroupinterna

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Pathology of Occupational Lung Disease by Andrew Churg, Francis H.Y. Green (Editor); ISBN: 0896401219; http://www.amazon.com/exec/obidos/ASIN/0896401219/icongroupinterna

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Patient's Health Maintenance Workbook for Lung Disease: A Guide to Self-Care and Healing by Brian C. Leutholtz; ISBN: 0849307333; http://www.amazon.com/exec/obidos/ASIN/0849307333/icongroupinterna

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Proteoglycans in Lung Disease (Lung Biology in Health and Disease, 168) by Hari G. Garg (Editor), et al (2002); ISBN: 0824708156; http://www.amazon.com/exec/obidos/ASIN/0824708156/icongroupinterna

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Psychosocial Aspects of Cystic Fibrosis: A Model for Chronic Lung Disease by Paul Patterson (1973); ISBN: 0930194330; http://www.amazon.com/exec/obidos/ASIN/0930194330/icongroupinterna

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Pulmonary Blood Vessels in Lung Disease (Progress in Respiration Research, Vol 26) by J. Widimsky (Editor) (1990); ISBN: 380555155X; http://www.amazon.com/exec/obidos/ASIN/380555155X/icongroupinterna

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Pulmonary Circulation in Chronic Lung Diseases by J. Widimsky (Editor), et al (1985); ISBN: 3805539614; http://www.amazon.com/exec/obidos/ASIN/3805539614/icongroupinterna

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Pulmonary emphysema and related lung diseases by Theodore Rodman; ISBN: 0801641403; http://www.amazon.com/exec/obidos/ASIN/0801641403/icongroupinterna

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Pulmonary Function Tests in Clinical and Occupational Lung Disease by Albert Miller (Editor); ISBN: 0808917242; http://www.amazon.com/exec/obidos/ASIN/0808917242/icongroupinterna

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Pulmonary Nuclear Medicine: Techniques in Diagnosis of Lung Disease (Lung Biology in Health and Disease, Vol 23) by Harold L. Atkins (Editor); ISBN: 0824772334; http://www.amazon.com/exec/obidos/ASIN/0824772334/icongroupinterna

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Right Ventricular Hypertrophy and Function in Chronic Lung Disease (1992); ISBN: 3540197745; http://www.amazon.com/exec/obidos/ASIN/3540197745/icongroupinterna

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Right Ventricular Hypertrophy and Function in Chronic Lung Disease (Current Topics in Rehabilitation) by V. Jezek, et al; ISBN: 0387197745; http://www.amazon.com/exec/obidos/ASIN/0387197745/icongroupinterna

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Silica and Silica-Induced Lung Diseases by Vincent Castranova (Editor), et al; ISBN: 0849347092; http://www.amazon.com/exec/obidos/ASIN/0849347092/icongroupinterna

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Surfactant Therapy for Lung Disease by Bengt Robertson (Editor), H. William Taeusch (Editor) (1995); ISBN: 0824795024; http://www.amazon.com/exec/obidos/ASIN/0824795024/icongroupinterna

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Surgical Pathology of Diffuse Infiltrative Lung Disease by Andrew Flint, Thomas V. Colby; ISBN: 0808918672; http://www.amazon.com/exec/obidos/ASIN/0808918672/icongroupinterna

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Surgical Pathology of Non-Neoplastic Lung Disease (1990); ISBN: 0721653014; http://www.amazon.com/exec/obidos/ASIN/0721653014/icongroupinterna

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The Health Consequences of Smoking: Chronic Obstructive Lung Disease (A Report of the Surgeon General); ISBN: 9997388283; http://www.amazon.com/exec/obidos/ASIN/9997388283/icongroupinterna

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To Air Is Human: A Manual for People With Chronic Lung Disease by Madeline H. Barrow, et al (1995); ISBN: 0939838265; http://www.amazon.com/exec/obidos/ASIN/0939838265/icongroupinterna

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Update Treatment of Multidrug-Resistant Tuberculosis: Proceedings of a Sponsored Symposium to the 29th World Conference of the International Union Against Tuberculosis and Lung Diseases (Iuatld/Uictmr) B (Chemotherapy) by Michael D. Iseman (Editor), Praparn Youngchaiyud (Editor) (1999); ISBN: 3805569246; http://www.amazon.com/exec/obidos/ASIN/3805569246/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “lung disease” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

A Two stage model for the determination of risk for chronic obstructive lung disease: final report Author: Speizer, Frank E.; Year: 1965; Boston, Mass.: Brigham and Women's Hospital, 1980

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Advances in chronic obstructive lung disease: proceedings of the World Congress on Asthma, Bronchitis & Conditions Allied held in New Delhi from 9-15 November, 1974 Author: Viswanathan, R. (Raman),; Year: 1971; Delhi: The Asthma and Bronchitis Foundation of India: sole distributors, Atma Ram, c1977

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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Assessment of a patient with lung disease Author: Webb, Jonathan R.; Year: 1976; Lancaster, England: Published in association with Update Publications by MTP Press, 1981; ISBN: 0852004265 http://www.amazon.com/exec/obidos/ASIN/0852004265/icongroupinterna

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Cardiorespiratory control: lung disease and systems analysis Author: Fokkens, Jelto Kornelis.; Year: 1966; [Utrecht: s.n., 1974?]

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Chronic lung disease and its prevention in Australia. Author: Royal Australian College of General Practitioners.; Year: 1980; Sydney: Royal Australian College of General Practitioners, [1971]

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Chronic obstructive lung disease Author: Balchum, Oscar J. (Oscar Joseph),; Year: 1972; Kansas City, Mo.: American family physician, 1977

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Clinical and physiological follow-up of severe chronic obstructive lung disease, by Astrid Brundin and Ritva Tammivaara-Hilty. Author: Brundin, Astrid.; Year: 1972; Copenhagen, Munksgaard, 1972; ISBN: 8716011562

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Current research in chronic obstructive lung disease; proceedings. Author: Chronic Respiratory Diseases Control Program (National Center for Chronic Disease Control); Year: 1968; Arlington, Va., National Center for Chronic

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Epidemiology of chronic non-specific lung disease (chronic bronchitis); a critical analysis of three field surveys of CNSLD carried out in the Netherlands. Author: Lende, R. van der.; Year: 1969; Assen, Van Gorcum, 1969

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Essays in heart and lung disease. Author: Foxwell, Arthur.; Year: 1895; London, Griffin, 1895

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Fighting the first cause of lung disease Author: American Lung Association.; Year: 1976; New York: The Association, [1975?]

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International Conference on Occupational Lung Diseases Author: Morgan, W. Keith C.; Year: 1967; Park Ridge, Ill.: American College of Chest Physicians, 1980

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Interstitial lung disease: the 18th Aspen Lung Conference Author: Filley, Giles F. (Giles Franklin),; Year: 1976; Park Ridge, Ill.: American College of Chest Physicians, 1976

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Lung disease [by] Duncan A. Holaday, with the assistance of Christen C. Rattenborg. Author: Holaday, Duncan A.; Year: 1967; Philadelphia, Davis [c1967]

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Management of acute respiratory failure in chronic obstructive lung disease Author: Gertz, Ingrid.; Year: 1980; [Stockholm?: s.n., 1976?]

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On loss of weight, blood-spitting, and lung disease. Author: Dobell, Horace,; Year: 1880; London, Churchill, 1880

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Respiratory and circulatory investigations in obstructive and restrictive lung disease Author: Gabriel, Senefro K.; Year: 1977; Stockholm: Distributed by Almquist; Wiksell, 1972

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Respiratory disease in a farming population: a serio-epidemiological survey of farmer's lung and chronic nonspecific lung disease among dairy farmers in Eastern Finland Author: Katila, Marja-Leena.; Year: 1981; Kuopio, Finland: Dept. of Clinical Microbiology, University of Kuopio, 1979; ISBN: 951780072X

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Serology of fungal infection and farmer's lung disease: a laboratory manual Author: Evans, E. Glyn V.; Year: 1977; [London]: British Society for Mycopathology, 1976

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The Natural history of chronic bronchitis and emphysema: an eight-year study of early chronic obstructive lung disease in working men in London Author: Fletcher, C. M. (Charles Montague),; Year: 1978; Oxford; New York: Oxford Univ. Press, 1976; ISBN: 0192611194

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http://www.amazon.com/exec/obidos/ASIN/0192611194/icongroupinterna •

The nature and varieties of destructive lung disease included under the term pulmonary consumption, as seen among soldiers and the hygienic conditions under which they occur. Author: Welch, Francis H.; Year: 1873; [London, Harrison, 1873?]

Chapters on Lung Disease In order to find chapters that specifically relate to lung disease, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and lung disease using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “lung disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on lung disease: •

Esophagitis and Barrett's Esophagus in Children Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume Two. Philadelphia, PA: Current Medicine. 1999. p. 1258-1262. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Gastroesophageal (GE) reflux is responsible for most cases of esophagitis in children. This chapter on esophagitis and Barrett's esophagus in children is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. This chapter focuses on the special features of reflux esophagitis as it pertains to children. The specific mechanisms that lead to reflux esophagitis in children are similar to those in adults, i.e., transient lower esophageal sphincter relaxations, hypotonic lower esophageal sphincter, poor esophageal clearance, hiatal hernia, and delayed gastric emptying. Certain underlying disorders predispose children to pathologic GE reflux: neurologic impairment, repaired esophageal atresia, chronic lung disease (especially cystic fibrosis), and hiatal hernia. As in adults, upper GI endoscopy usually is the definitive study to determine the presence of esophagitis or Barrett's esophagus. In nonerosive reflux esophagitis, symptoms usually respond to measures such as lifestyle changes and prokinetic drugs or H2 receptor antagonists. Erosive esophagitis usually is chronic and relapsing, with the risk of stricture formation, and usually requires antireflux surgery or long term proton pump inhibitor use. Barrett's esophagus (BE), the presence of precancerous cells in the esophagus, is much less prevalent in children than in adults, and in childhood BE there is a high prevalence of serious, underlying coexisting disorders. Comorbidities can include neurologic impairment, chronic lung disease, esophageal atresia, and problems arising from chemotherapy for malignancies. 1 table. 27 references.

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Respiratory Disorders Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 154-172.

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Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail: [email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Respiratory disorders are common and may significantly affect dental treatment, especially general anesthesia. Respiratory diseases are often also a contraindication to opioids, benzodiazepines and other respiratory depressants. This chapter on respiratory disorders is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include upper respiratory tract viral infections, sinusitis, lower respiratory tract infections, pulmonary tuberculosis, Legionnaire's disease (legionellosis), lung abscess, bronchiectasis, cystic fibrosis, chronic obstructive airways diseases, asthma, bronchogenic carcinoma (lung cancer), occupational lung disease, sarcoidosis, postoperative respiratory complications (including aspiration of gastric contents), obstructive sleep apnea syndrome, and respiratory distress syndromes (RDS). For each disease, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 1 figure. 5 tables. 51 references. •

Abdominal Approach to Apical Prolapse Source: in Carlin, B.I. and Leong, F.C., eds. Female Pelvic Health and Reconstructive Surgery. New York, NY: Marcel Dekker, Inc. 2003. p. 281-289. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $185.00 plus shipping and handling. ISBN: 0824708229. Summary: The support system of the pelvis is made up of three major components: muscles, nerves, and connective tissue or endopelvic fascia. Both direct trauma (e.g., vaginal childbirth) and indirect trauma (e.g., chronic lung disease) to these important structures can disrupt the integrity of the pelvic floor and predispose a patient to pelvic organ prolapse. Connective tissue abnormalities and certain neurological disorders may also place certain patients at higher risk for development of pelvic organ prolapse. This chapter on the abdominal approach to apical prolapse is from a textbook that provides comprehensive, authoritative coverage of female pelvic health and reconstructive surgery. The authors discuss anatomy, etiology, and pathophysiology; the surgical approach to apical prolapse, including abdominal sacrocolpopexy, and the choice of graft material; laparoscopic procedures; and other abdominal surgeries, including abdominal sacrocolpoperineopexy and abdominal sacrospinous ligament suspension. The authors conclude that management of vaginal vault prolapse includes a variety of vaginal, transabdominal, and laparoscopic techniques. 36 references. 4 tables.

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Organ Involvement: Pulmonary Source: in Clements, P.J.; Furst, D.E., Eds. Systemic Sclerosis. Baltimore, MD: Williams and Wilkins. 1996. p. 299-331. Contact: Available from Williams and Wilkins, Special Sales Department. (800) 358-3583. Summary: This chapter for health professionals focuses on the clinical manifestations of pulmonary involvement in systemic sclerosis (SSc). SSc produces fibrosing alveolitis or primary pulmonary vascular disease within the lungs. The pathogenesis of these two patterns of abnormality within the lungs of SSc patients is explained. Common pathological findings in fibrosis and pulmonary vascular disease are described. The clinical features of pulmonary disease in SSc are presented, focusing on the features of

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fibrosing alveolitis and pulmonary arterial hypertension. Other pulmonary complications are highlighted. The prognosis of lung disease in SSc patients is discussed. Methods of assessing pulmonary involvement in SSc are described, including blood tests, radiographic techniques, radionuclide imaging, lung function tests, bronchoalveolar lavage, lung biopsy, and pulmonary vascular investigations. Methods of treating pulmonary SSc are reviewed. 203 references, 7 figures, and 5 tables. •

Management of the Medically Compromised Patient Source: in Kwon, P.H. and Laskin, D.M. Clinician's Manual of Oral and Maxillofacial Surgery. Chicago, IL: Quintessence Publishing Co, Inc. 2001. p. 227-262. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $58.00 plus shipping and handling. ISBN: 0867153962. Summary: This chapter on management of the medically compromised patient is from a spiral-bound handbook that offers quick reference information to the oral and maxillofacial surgeon. The outline and chart-based format is designed to offer quick access to information that may be needed in situations that do not allow time for a leisurely perusal of textbooks and journals. The chapter covers cardiac disease, including coronary artery disease, congestive heart failure, dysrhythmias and conduction disturbances, valvular heart disease, prosthetic valves, and congenital heart disease; respiratory disease, including obstructive lung disease (chronic obstructive pulmonary disease and asthma) and infiltrative diseases of the lung; renal (kidney) disease, including the four different stages of chronic renal failure and acute renal failure; hypertension (high blood pressure); blood disorders, including anemia, erythrocytosis, leukocyte disorders, platelet disorders, coagulation disorders, and causes of bleeding disorders; endocrine diseases, notably diabetes mellitus; adrenal disease; thyroid disease; pituitary disease; neurological diseases, including cerebrovascular disease (including stroke), seizure disorders, and neuromuscular diseases; liver disease; autoimmune diseases; and the immunocompromised patient. For each condition, the chapter discusses preoperative evaluation, history, physical examination, laboratory examinations, preoperative therapy, and perioperative monitoring. 3 tables.

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Chapter 28: Sarcoidosis Source: in Klippel, J.H., et al., eds. Primer on the Rheumatic Diseases. 12th ed. Atlanta, GA: Arthritis Foundation. 2001. p. 455-458. Contact: Available from Arthritis Foundation. P.O. Box 1616, Alpharetta, GA 300091616. (800) 207-8633. Fax (credit card orders only) (770) 442-9742. Website: www.arthritis.org. PRICE: $69.95 plus shipping and handling. ISBN: 0912423293. Summary: This chapter provides health professionals with information on the pathogenesis, clinical features, diagnosis, and management of sarcoidosis. This systemic, chronic, granulomatous disease of unknown etiology mainly affects young adults in their 20s and 30s. Although the disease occurs in all ethnic groups, it is most common in African Americans and Caucasians of northern European descent. The disease is slightly more common in women than in men. Although the cause of sarcoidosis is unknown, the immune response has a central role in its pathogenesis. Respiratory symptoms are the most common presenting complaints, and the majority of patients, regardless of initial symptoms, have abnormal findings on chest radiographs. Other common clinical features include asymptomatic hilar adenopathy detected on chest roentgenogram,

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constitutional symptoms, rheumatic manifestations such as arthritis, and extrathoracic inflammation. There is no single finding or laboratory test that establishes the diagnosis, so it depends on compatible clinical features involving at least two organ systems, histologic evidence of noncaseating granulomas, and exclusion of other possible causes. In a patient who does not have specific skin or conjunctival lesions, transbronchial lung biopsy is the preferred diagnostic test. Skin anergy is a typical feature; however, it is not diagnostic. Treatment is dependent on the specific manifestations. Corticosteroids are used to treat severe lung disease, liver disease, hypercalcemia, cardiac inflammation, posterior uveitis, neurosarcoidosis, and severe sarcoidosis of other organs. Other potentially useful drugs include nonsteroidal antiinflammatory drugs, colchicine, chloroquine, hydroxychloroquine, methotrexate, and cyclosporine. 1 figure, 1 table, and 20 references.

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CHAPTER 7. MULTIMEDIA ON LUNG DISEASE Overview In this chapter, we show you how to keep current on multimedia sources of information on lung disease. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Bibliography: Multimedia on Lung Disease The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in lung disease (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on lung disease: •

Acute diffuse lung diseases [videorecording]: therapeutic aspects Source: Academy of Health Sciences; [made by] TV Branch, Health Sciences Media Division, AHS, USA; Year: 1976; Format: Videorecording; Fort Sam Houston, Tex.: The Academy: [for sale by its Health Sciences Media Division], 1976

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Chronic lung disease: management [slide] Source: by Ben V. Branscomb; Year: 1975; Format: Slide; Park Ridge, Ill.: American College of Chest Physicians; [Chicago: for sale by its Dept. of Multimedia Communications], c1975

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Chronic obstructive lung disease [videorecording]: the theophyllines Source: Intercollegiate Center for Nursing Education; Year: 1986; Format: Videorecording; Spokane, Wash.: I.C.N.E., c1986

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Clinical applications and utility of high resolution CT in lung disease [videorecording] Source: the Radiological Society of North America; Year: 1993; Format: Videorecording; [Oak Brook, Ill.]: RSNA, c1993

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Diffuse lung disease [slide]: radiologic and physiologic correlations Source: the Radiological Society of North America; Year: 1990; Format: Slide; Oak Brook, Ill.: RSNA, c1990

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Early differential diagnosis and treatment of lung disease [videorecording] Source: moderator, Stephen I. Rennard; panelists, Dennis E. Doherty, Nicholas Gross, Faroque A. Kahn; Year: 1997; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1997

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Environmental lung disease [videorecording] Source: presented by the Department of Medicine, Emory University, School of Medicine; Year: 1987; Format: Videorecording; Atlanta, Ga.: The University, c1987

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Imaging of diffuse lung disease Source: David A. Lynch, John D. Newell, Jr., Jin Seong Lee; Year: 2000; Format: Edited by; Hamilton, Ontario; Lewiston, NY: B.C. Decker, c2000

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Interstitial lung disease Source: Marvin I. Schwarz, Talmadge E. King, Jr; Year: 1998; Format: Edited by; Hamilton, Ont.: B. C. Decker, c1998

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Interstitial lung disease Source: Marvin I. Schwarz, Talmadge E. King, Jr; Year: 2003; Format: Edited by; Hamilton, Ontario: B.C. Decker, 2003

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Interstitial lung disease, clinical assessment and differential diagnosis [slide] Source: produced by Biomedical Communications, University of Arizona, Health Sciences Center; presented by the American Thoracic Society, American Lung Association, ALA/ATS Commi; Year: 1989; Format: Slide; [New York, N.Y.]: American

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Interstitial lung disease, overview [slide] Source: produced by Biomedical Communications, University of Arizona, Health Sciences Center; presented by the American Thoracic Society, American Lung Association, ALA/ATS Committee on Learning Resources; Year: 1989; Format: Slide; [New York, N.Y.]: American

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Lifeline to the lungs: the role of respiratory therapy in chronic obstructive lung disease [motion picture] Source: Peter Safar; produced by John Branigan; Year: 1972; Format: Motion picture; New York: Winthrop Laboratories, 1972

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Neonatal lung disease [slide] Source: [J. Thomas Stocker]; Year: 1983; Format: Slide; Gainesville, Fla.: Editorial Enterprises Corp., c1983

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New light on obstructive lung disease [slide] Source: Department of Medical Education at the Millard Fillmore Hospital, in cooperation with the School of Medicine, State University of New York at Buffalo; Year: 1976; Format: Slide; Buffalo: Communications in Learning, 1976

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Organic dust induced lung disease [videorecording] Source: Marshfield Medical Foundation, in cooperation with Marshfield Clinic and St. Joseph's Hospital; [presented by] Marshfield Video Network; Year: 1985; Format: Videorecording; Marshfield, WI: The Foundation, 1985

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PFT, obstructive lung disease [electronic resource]: programmed instructional package. Year: 1985; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1985

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PFT, restrictive lung disease [electronic resource]: programmed instructional package. Year: 1985; Format: Electronic resource; Edwardsville, KS: Medi-Sim, c1985

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Practical approaches to infant lung disease [sound recording] Source: American Academy of Pediatrics; Year: 1989; Format: Sound recording; Chicago, IL: Teach'em, [1989]

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PulMeDx [electronic resource]: computer-based learning in occupational and environmental lung disease: a case-based approach Source: Health Sciences Consortium; [developed by the Department of Community and Preventive Medicine of the Medical College ofPennsy; Year: 1996; Format: Electronic resource; Chapel Hill, NC: Health Sciences Consortium, [1996?]

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Radiologic-pathologic correlations in interstitial lung disease [videorecording] Source: Radiological Society of North America; Year: 1985; Format: Videorecording; [Chicago, Ill.]: The Society, [1985]

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Respiratory care for lung disease in women [videorecording]: new research evidence Source: [presented by] Primedia Healthcare; Year: 2003; Format: Videorecording; Carrollton, TX: Primedia Workplace Learning, c2003

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Surfactant physiology and its application to lung disease in the newborn [videorecording] Source: [presented by] Marshfield Video Network, in cooperation with Marshfield Medical Research Foundation, Marshfield Clinic, [and] St. Joseph's Hospital; Year: 1987; Format: Videorecording; Marshfield, WI: The Network, c1987

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Surgery, anesthesia and chronic obstructive lung disease [slide] Source: University of Michigan, Medical Center, Independent Study Unit, Dept. of Postgraduate Medicine and Health Professions Education; Year: 1975; Format: Slide; Ann Arbor: The University: [for loan or sale by its Medical Center Media Library], c1975

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The health consequences of smoking [electronic resource]: chronic obstructive lung disease: a report of the Surgeon General. Year: 1984; Format: Electronic resource; Rockville, Md.: U.S. Dept. of Health and Human Services, Public Health Service, Office on Smoking and Health; Washington, D.C.: For sale by the Superintendent of Documents, U.S. Government Printing Office, 1984

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The Radiology of thoracic trauma and occupational lung disease [videorecording] Source: the Radiological Society of North America; Year: 1993; Format: Videorecording; [Oak Brook, Ill.]: RSNA, c1993

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CHAPTER 8. PERIODICALS AND NEWS ON LUNG DISEASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lung disease.

News Services and Press Releases One of the simplest ways of tracking press releases on lung disease is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “lung disease” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to lung disease. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “lung disease” (or synonyms). The following was recently listed in this archive for lung disease: •

Nitric oxide may reduce lung disease and death in premature infants with RDS Source: Reuters Medical News Date: November 26, 2003

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Nitric oxide may help preemies with lung disease Source: Reuters Health eLine Date: November 26, 2003

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Rifamycin-sparing regimen shows promise in mycobacterial lung disease Source: Reuters Medical News Date: November 17, 2003

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Deaths from chronic lung disease underestimated Source: Reuters Health eLine Date: October 28, 2003

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Diet boost doesn't speed rehab in lung disease Source: Reuters Health eLine Date: September 18, 2003

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European smokers will see images of lung disease Source: Reuters Medical News Date: September 08, 2003

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Glaxo lung disease drug rejected by FDA advisers Source: Reuters Health eLine Date: September 05, 2003

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Older drugs still useful for lung disease patients Source: Reuters Health eLine Date: July 18, 2003

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Preterm delivery and chronic lung disease linked with persistent cognitive deficits Source: Reuters Medical News Date: March 07, 2003

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Job exposure linked to many cases of lung disease Source: Reuters Health eLine Date: October 31, 2002

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Lung diseases in Europe cost $100 billion-report Source: Reuters Health eLine Date: September 17, 2002

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Refillable oxygen tanks helpful for lung disease Source: Reuters Health eLine Date: September 05, 2002

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Drug may improve survival in fatal lung disease Source: Reuters Health eLine Date: August 26, 2002

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Bacterial newcomers can worsen lung disease Source: Reuters Health eLine Date: August 14, 2002

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Nurses provide effective care for chronic lung disease Source: Reuters Health eLine Date: August 01, 2002

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Flavoring ups lung disease risk in popcorn factory Source: Reuters Health eLine Date: July 31, 2002

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Clues to how inhaled steroids help lung disease Source: Reuters Health eLine Date: June 27, 2002

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Hospitalization often due to respiratory virus infection in lung disease patients Source: Reuters Medical News Date: June 11, 2002

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Canadian researchers identify new infant lung disease Source: Reuters Medical News Date: June 11, 2002

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Canada team identifies new infant lung disease Source: Reuters Health eLine Date: June 11, 2002

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Popcorn flavor spurs factory workers' lung disease Source: Reuters Health eLine Date: April 25, 2002

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Lung disease patients should see doc before flight Source: Reuters Health eLine Date: March 28, 2002

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Combination regimen effective against systemic sclerosis lung disease Source: Reuters Medical News Date: March 07, 2002

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Spectrum of HIV-related lung diseases has changed with HAART Source: Reuters Medical News Date: January 08, 2002

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UK smokers ignore possible lung disease symptoms Source: Reuters Health eLine Date: January 07, 2002

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Exercise may sharpen lung disease patients' minds Source: Reuters Health eLine Date: December 28, 2001

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Risk factors for lung disease after stem cell transplantation identified Source: Reuters Medical News Date: December 07, 2001

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

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Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “lung disease” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “lung disease” (or synonyms). If you know the name of a company that is relevant to lung disease, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “lung disease” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “lung disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on lung disease: •

Smoking and Periodontal Disease, Tooth Loss, and Dental Caries Source: Oral Care Report. 13(1): 4,8. 2003. Contact: Available from Oral Care Report. c/o Dr. Chester W. Douglass, Department of Oral Health Policy, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115. Fax (617) 432-0047. E-mail: [email protected]. Website: www.colgateprofessional.com (full-text available online). Summary: Apart from the established associations between smoking and serious illnesses such as cancer, heart disease and lung disease, oral health problems are also linked to smoking. Numerous studies report an increased risk for periodontal disease,

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tooth loss, and dental caries in smokers as compared to nonsmokers. This brief article explores this association, focusing on tooth loss, probing attachment loss, and dental caries in smokers. The authors consider the potential mechanisms by which smoking affects dental status, noting that said mechanisms are not well understood. 1 table. 3 references. •

Update on Management of Scleroderma Source: Bulletin on the Rheumatic Diseases. 49(10): 1-4. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on the management of scleroderma. This chronic disease targets the skin, heart, lungs, gastrointestinal tract, kidneys, muscles, and joints. Scleroderma is classified into limited and diffuse cutaneous forms. Almost all patients with scleroderma have Raynaud's phenomenon (RP). The most effective way to prevent RP is to avoid exposure to cold. Calcium channel blockers are currently the most effective and safest vasodilators for scleroderma related RP. Other useful medications include coated aspirin and intravenous prostaglandins. Options for managing gastrointestinal disease include elevating the head of the bed, using antacids, making dietary changes, and taking oral motility agents. Prostaglandins and their analogs are now available to treat pulmonary hypertension. Immunosuppressive agents can be useful in treating interstitial lung disease. Renal disease can be treated with angiotensin converting enzyme inhibitors. Disease modifying agents that can be used to treat early diffuse scleroderma include colchicine, paraaminobenzoic acid, and D-penicillamine. Other drugs that have been investigated for treating early diffuse scleroderma include relaxin, halofuginone, glucocorticoids, methotrexate, thalidomide, and cyclophosphamide. People who have scleroderma are more likely to experience major depression, so good pain control and the use of antidepressants are important. 1 table and 12 references.

•

Pulmonary Manifestations of SLE Source: Lupus News. 20(2): 18-19. Spring 2000. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article provides people who have lupus with information on its pulmonary manifestations. The prevalence of lung involvement in people with lupus is very high. Lupus manifestations within the lung parenchyma include infections, pneumonitis, interstitial lung disease (ILD), diffuse alveolar hemorrhage, and acute reversible hypoxia syndrome. Infection is the most common cause of an abnormal chest x ray involving the lung parenchyma. People who have lupus are susceptible to infections because their immune system functions abnormally and because the medications they use decrease the ability to resist infection. Infections are caused by bacteria, viruses, fungi, and parasites. Pneumonitis, noninfectious pneumonia, is a form of inflammation within the alveoli that is not associated with infection. ILD is inflammation within the interstitium, which leads to fibrosis in the area if the inflammation persists. Diffuse alveolar hemorrhage is a severe and life threatening complication of lupus and probably reflects vasculitis of the pulmonary blood vessels. Acute reversible hypoxia causes shortness of breath from low oxygen within the blood. Fifty to eighty percent of people who have lupus develop inflammation of the lining

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around the lungs and the heart, causing fluid to accumulate around these organs. Blood clot formation or elevation of the blood pressure within the pulmonary arteries may also occur in people who have lupus. In rare cases, pulmonary neuromuscular system involvement in lupus can cause shrinking lung syndrome. Drugs used to treat lupus may also have pulmonary side effects. 1 figure.

Academic Periodicals covering Lung Disease Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lung disease. In addition to these sources, you can search for articles covering lung disease that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for lung disease. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with lung disease. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to lung disease: Acetylcysteine •

Inhalation - U.S. Brands: Mucomyst; Mucomyst-10; Mucosil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202007.html

Bronchodilators, Adrenergic •

Inhalation - U.S. Brands: Adrenalin Chloride; Airet; Alupent; Arm-a-Med Isoetharine; Arm-a-Med Metaproterenol; Asthmahaler Mist; AsthmaNefrin; Beta2; Brethaire; Bronkaid Mist; Bronkaid Suspension Mist; Bronkometer; Bronkosol; Dey-Lute Isoetharine; Dey-Lute Metaproterenol; Isupr http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202095.html

•

Oral/Injection - U.S. Brands: Adrenalin; Alupent; Ana-Guard; Brethine; Bricanyl; EpiPen Auto-Injector; EpiPen Jr. Auto-Injector; Isuprel; Proventil; Proventil Repetabs; Ventolin; Volmax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202096.html

Ipratropium •

Inhalation - U.S. Brands: Atrovent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202304.html

Ipratropium and Albuterol •

Inhalation-Local - U.S. Brands: Combivent; DuoNeb http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203487.html

Palivizumab •

Systemic - U.S. Brands: Synagis http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203646.html

Respiratory Syncytial Virus Immune Globulin Intravenous •

Systemic - U.S. Brands: RespiGam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203069.html

Theophylline, Ephedrine, and Hydroxyzine •

Systemic - U.S. Brands: Marax; Marax-DF http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202555.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Researching Medications

191

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.

Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to lung disease by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “lung disease” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for lung disease: •

Pyruvate http://www.rarediseases.org/nord/search/nodd_full?code=1087

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•

Pyruvate http://www.rarediseases.org/nord/search/nodd_full?code=1122

•

Flemington, NJ 08822 http://www.rarediseases.org/nord/search/nodd_full?code=1195

•

DMP 777 http://www.rarediseases.org/nord/search/nodd_full?code=435

If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

195

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “lung disease” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “lung disease” (or synonyms) into the “For these words:” box. The following is a sample result: •

Linguistic and Cultural Aspects of Tuberculosis Screening and Management for Refugees and Immigrants Contact: University of Washington, AIDS Clinical Trials Unit, Harborview Medical Center, (206) 731-3184, http://www.depts.washington.edu/~actu/. Summary: This is the transcript of a presentation made at the International Union Against Tuberculosis (TB) and Lung Disease Conference held in Chicago, Illinois in March 1996. The presentation focuses on TB screening and management of active cases in the context of communication issues across linguistic and cultural differences between biomedicine and non-western cultures. The speaker offers strategies for managing chronic problems in TB treatment and prophylaxis in the multicultural setting, explains why translation and patient education is a complex process, and outlines a system for negotiating cultural differences.

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lung disease” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.

15 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 391663 1972 2210 300 14 396159

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “lung disease” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on lung disease can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to lung disease. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to lung disease. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “lung disease”:

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•

Other guides Bronchitis http://www.nlm.nih.gov/medlineplus/bronchitis.html COPD http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.t ml Lung Cancer http://www.nlm.nih.gov/medlineplus/lungcancer.html Pulmonary Fibrosis http://www.nlm.nih.gov/medlineplus/pulmonaryfibrosis.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html

Within the health topic page dedicated to lung disease, the following was listed: •

General/Overviews JAMA Patient Page: Lung Disease Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ06T60NAC &sub_cat=577 Lung Disease Source: National Women's Health Information Center http://www.4woman.gov/faq/lung_disease.htm

•

Diagnosis/Symptoms Blood Gas Tests Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/blood_gases/test.html Bronchoscopy: Pulmonary Branch Protocols Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/pepubs/bronchoscopy.pdf Chest Pain, Acute: Self-Care Flowcharts Source: American Academy of Family Physicians http://familydoctor.org/flowcharts/523.html Radiography -- Chest (Chest X-ray) Source: American College of Radiology, Radiological Society of North America http://www.radiologyinfo.org/content/chest_radiography.htm Spirometry Source: National Lung Health Education Program http://www.nlhep.org/spirom1.html

Patient Resources

•

Treatment Cleaning of Portable Humidifiers and Vaporizers at Home Source: National Jewish Medical and Research Center http://www.nationaljewish.org/medfacts/cleaning.html

•

Coping Coping with Indoor Air Pollution Source: American Association for Respiratory Care http://www.aarc.org/patient_education/tips/inpoll.html Minimizing the Effects of Outdoor Air Pollution Source: American Association for Respiratory Care http://www.aarc.org/patient_education/tips/outpoll.html Traveling with Oxygen: Planning Is Key Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01555

•

Specific Conditions/Aspects Adult (Acute) Respiratory Distress Syndrome (ARDS) Source: American Lung Association http://www.lungusa.org/diseases/ards_factsheet.html Bronchiectasis Source: American Lung Association http://www.lungusa.org/diseases/bronchiectasis.html Collapsed Lung (Pneumothorax) Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01228 Facts about Beryllium Disease Source: National Jewish Medical and Research Center http://www.nationaljewish.org/medfacts/beryllium_medfact.html Forest Fires and Respiratory Health Source: American Lung Association http://www.lungusa.org/diseases/wildfires.html Goodpasture's Syndrome Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/goodpasture/index.htm Hantavirus Pulmonary Syndrome Source: American Lung Association http://www.lungusa.org/diseases/hantavirus_factsheet.html Hot Tub Lung Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00660 Hyperinflated Lungs Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00684

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Occupational Respiratory Diseases: Your Workplace and Your Lungs Source: American Academy of Family Physicians http://familydoctor.org/handouts/134.html Passive Smoke Source: National Jewish Medical and Research Center http://www.nationaljewish.org/medfacts/passive.html Pleurisy Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00244 Pulmonary Edema Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00412 Respiratory Failure Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/res_fail.pdf Spontaneous Pneumothorax Source: American Lung Association http://www.lungusa.org/diseases/pneumothorax.html •

Children Bronchopulmonary Dysplasia Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/bpd/toc.htm Helping Your Child Breathe Easier Source: American Association for Respiratory Care http://www.aarc.org/patient_education/tips/kids.html JAMA Patient Page: Your Child's Respiratory Health Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZQOCATIAC &sub_cat=577 Looking at Your Lungs Source: Nemours Foundation http://kidshealth.org/kid/body/lungs_noSW.html Primary Ciliary Dyskinesia Source: American Lung Association http://www.lungusa.org/diseases/pcd.html Respiratory Distress Syndrome of the Newborn Source: American Lung Association http://www.lungusa.org/diseases/rdsfac.html Transient Tachypnea of the Newborn (TTN) Source: Nemours Foundation http://kidshealth.org/parent/medical/lungs/ttn.html

Patient Resources

•

205

From the National Institutes of Health Lungs in Health and Disease Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/public/lung/other/lungs_hd.pdf What Is ARDS (Acute Respiratory Distress Syndrome)? Source: National Heart, Lung, and Blood Institute http://dci.nhlbi.nih.gov/Diseases/Ards/Ards_WhatIs.html

•

Latest News Reflux Link to Airway Problems in Kids Unclear Source: 11/24/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14807 .html

•

Organizations American College of Chest Physicians http://www.chestnet.org/ American Lung Association http://www.lungusa.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/ National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/ National Lung Health Education Program http://www.nlhep.org/

•

Pictures/Diagrams Atlas of the Body: The Respiratory System -- Structure Detail Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ8PPLCGJC &sub_cat=285 How the Body Works: The Respiratory System Source: Nemours Foundation http://kidshealth.org/misc_pages/bodyworks/resp.html

•

Statistics African Americans and Lung Disease Source: American Lung Association http://www.lungusa.org/diseases/africanlung_factsheet.html Asian Americans/Pacific Islanders and Lung Disease Source: American Lung Association http://www.lungusa.org/diseases/asianlung_factsheet.html

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Hispanics and Lung Disease Source: American Lung Association http://www.lungusa.org/diseases/hispaniclung_factsheet.html Minority Lung Disease Data 2000 Source: American Lung Association http://www.lungusa.org/pub/minority/mldd_00.html New Edition of Lung Disease Data Report Updates Resource with Newest Available Statistics Source: National Institute for Occupational Safety and Health http://www.cdc.gov/niosh/worldre02.html State-by-State Lung Disease Trend Report April 2001 Source: American Lung Association http://www.lungusa.org/data/s2s/s2s_index.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on lung disease. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Alpha 1 Antitrypsin Deficiency Source: Toronto, Ontario: Canadian Liver Foundation. 200x. 3 p. Contact: Available from Canadian Liver Foundation. Suite 1500, 2235 Sheppard Avenue East, Toronto Ontario, M2J 5B5. (416) 491-3353 or (800) 563-5483. Fax (416) 491-4952. Email: [email protected]. Website: [email protected]. PRICE: Full-text available online at no charge; Contact organization for print copies. Summary: Alpha 1 antitrypsin deficiency is an inherited condition occurring in approximately 1 in 5,000 live births. In this condition, the body produces abnormal alpha 1 antitrypsin with no protective activity and the liver releases insufficient amounts. As a consequence, the enzyme trypsin in the body not only breaks down proteins in foods but also attacks various body tissues. This can lead to liver disease in young children or to lung disease in young adults. This fact sheet, from the Canadian Liver Foundation, reviews alpha 1 antitrypsin deficiency. Written in question-andanswer format, the fact sheet covers the causes of alpha 1 antitrypsin deficiency, the risks of developing liver disease with this condition, symptoms of liver disease,

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diagnostic strategies, and treatment options. The fact sheet concludes with the contact information for the Canadian Liver Foundation (www.liver.ca or 800-563-5483). •

Basics of Alpha 1-Antitrypsin Deficiency Source: Minneapolis, MN: Alpha 1 Association. 1999. [4 p.]. Contact: Available from Alpha 1 Association. 8120 Penn Avenue, South, Suite 549, Minneapolis, MN 55431-1326. (800) 521-3025 or (612) 703-9979. Fax (612) 703-9977. Email: [email protected]. Website: www.alpha1.org. PRICE: $0.25 plus shipping and handling; bulk copies available. Summary: This brochure describes Alpha 1 antitrypsin deficiency (A1AD or Alpha 1), a genetic disorder that affects infants, children, and adults. It is the most common metabolic disorder that causes liver disease in infants and children; the disorder also causes cirrhosis and cancer of the liver in adults. The brochure reviews the functions of the liver, the causes of the deficiency, modes of inheritance, screening for A1AD, and symptoms in children and adults (including lung and liver disease and a skin disease called panniculitis). Alpha 1 antitrypsin (AAT) is a protein primarily manufactured in the liver and then released into the blood. The normal function of AAT is to protect body tissues from being damaged by neutrophil elastase, a protein found in white blood cells. The backup of abnormal AAT in the liver can cause liver damage. Screening for A1AD is done through a simple blood test. Lung disease is the most common manifestation of A1AD, with emphysema the most prevalent of the lung diseases. Liver disease is the second most common manifestation of AAT deficiency; it may cause chronic hepatitis or cirrhosis. No specific therapy for A1AD liver disease is available but rather involves supportive management for liver dysfunction and prevention of complications. Liver transplantation may be recommended for severe liver disease. The brochure concludes with contact information for the Alpha 1 Association and a form readers can request more information. 1 figure. 4 references.

•

Feeding and Swallowing Problems in Children Source: Rockville, MD: American Speech-Language-Hearing Association (ASHA). 200x. [2 p.]. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org. PRICE: $4.00 for 10, plus shipping and handling. Item Number: 0112337. Summary: This brochure describes dysphagia (swallowing dysfunction) in children and the importance of having dysphagia accurately diagnosed and treated. The brochure first explains the three phases of swallowing disorders, the oral phase, the pharyngeal phase, and the esophageal phase. The brochure than lists some causes of feeding and swallowing problems in children, and reviews the signs and symptoms of these problems. The brochure cautions that feeding and swallowing problems in children can result in dehydration or poor nutrition, the risk of aspiration (food or liquid entering the airway), pneumonia or repeated upper respiratory infections that can lead to chronic lung disease, and embarrassment or isolation in social situations involving eating. Readers are encouraged to consult a physician about the possible cause of the swallowing problem. A certified speech language pathologist can perform an evaluation of feeding and swallowing and provide treatment if appropriate. The brochure outlines the steps that the speech language pathologist may utilize in the evaluation and

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treatment of a child with swallowing problems. The contact information for the American Speech Language Hearing Association (ASHA) is provided. •

Give Your Legs a Rest Source: Atlanta, GA: Pritchett and Hull Associates, Inc. 1997. [2 p.]. Contact: Available from Pritchett and Hull Associates, Inc. 3440 Oakcliff Road, NE, Suite 110, Atlanta, GA 30340-3079. (800) 241-4925 or (770) 451-0602. Fax (800) 752-0510. Website: www.p-h.com. PRICE: $20.00 for a pack of 50; plus shipping and handling. Summary: This brochure describes restless legs syndrome (RLS) and offers self care suggestions for coping with the condition. RLS is a crawling, creeping, tingling, or aching feeling in the lower legs, upper legs, or arms that can come and go. RLS is very uncomfortable and can be painful for some people. RLS can prevent sleep because of the need to move the legs. The brochure lists the risk factors that can make RLS worse and briefly discusses the potential causes of the condition. RLS may get worse when one has a lot of caffeine, is pregnant, smokes, is very tired, is exposed to cold for a long time, has a lot of stress, or stays in one position for too long. RLS can be caused by medical problems such as diabetes, anemia, arthritis, or lung disease; a lack of vitamins or minerals; use of certain medications; or heredity. The brochure notes that medical treatment (medicines) can be helpful, particularly if a medical problem is causing the RLS. The brochure includes a section about periodic limb movement disorder (PLMD), a condition in which the leg or arm jerks during sleep. This disturbs the person's sleep, even though he or she may not be aware of it. The brochure is illustrated with cartoon line drawings and includes blank space for the reader to take notes or record questions to ask the physician.

•

Cigars: What's It Going to Cost You? Source: Waco, TX: HEALTH EDCO. 1997. [4 p.]. Contact: Available from HEALTH EDCO. P.O. Box 21207, Waco, TX 76702-1207. (800) 299-3366 or (817) 776-6461. Fax (888) 977-7653. E-mail: [email protected]. Website: www.healthedco.com. PRICE: $2.00; bulk copies available. Order number JG38098. Summary: This brochure offers young adults the chance to consider cigar advertising and more easily identify the myths such advertising perpetuates. The brochure first debunks five myths: cigars are safer than cigarettes, not inhaling prevents cancer, smoking cigars is sophisticated and cool, cigars are a power symbol, and secondhand smoke is harmless. The brochure then discusses how the cigar advertisements use manipulation and deception to entice viewers, particularly young adults, to smoke cigars. The brochure emphasizes that none of the advertisements depict the pain and suffering of losing a jaw or a life to mouth or throat cancer. The brochure then lists the personal costs of cigar smoking, including short term (bad breath, stained teeth, premature wrinkling, and high blood pressure), and long term (oral cancer, birth defects, heart attack, stroke, and lung disease). The brochure concludes with the contact information, including websites, of four resource organizations: the American Lung Association, the American Cancer Society, the American Heart Association, and the Office on Smoking and Health at the CDC.

•

Information About Albinism: Hermansky-Pudlak Syndrome Source: Philadelphia, PA: National Organization for Albinism and Hypopigmentation (NOAH). 199x. 2 p.

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Contact: National Organization for Albinism and Hypopigmentation. 1530 Locust Street, Number 29, Philadelphia, PA 19102-4415. (800) 473-2310 or (215) 545-2322. E-mail: [email protected]. Website: www.albinism.org. PRICE: Single copy free; donation or membership requested. Summary: This fact sheet provides information about Hermansky-Pudlak Syndrome (HPS) to health professionals and people who have albinism. HPS is a type of albinism that results in a tendency to bleed and to have lung disease. The severity and onset of HPS vary considerably, and its course is unpredictable. HPS is difficult to diagnose, but it should be suspected in any child with albinism who shows easy bruising or unusual bleeding. The color of skin and hair varies in HPS, and it may resemble any other type of albinism. Eye color varies from blue to brown, and eye problems are similar to those in other types of albinism. The bleeding problems of HPS result from a lack of dense bodies in platelets. In addition, some people who have HPS have less of a blood clotting substance called von Willebrand factor. Many people who have HPS have pulmonary fibrosis. In addition, they may have inflammatory bowel disease. The fact sheet lists a source of contact and identifies articles for professionals. •

Acid-Fast Direct Smear Microscopy Contact: US Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Center for HIV STD and TB Prevention, Division of Tuberculosis Elimination, 1600 Clifton Rd NE MS E10, Atlanta, GA, 30333, (404) 639-8135, http://www.cdc.gov/nchstp/tb/. Summary: This information kit presents a laboratory training program for laboratory technicians who perform or supervise direct acid-fast bacilli (AFB) microscopy sputum testing for tuberculosis (TB). It uses the methods and practices recommended by the World Health Organization (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD). The information kit explains the merits of AFB and discusses the mode of transmission of TB to emphasize the danger of working with the disease and the importance of biosafety in the laboratory. It explains specimen collection, laboratory arrangement, transportation and labeling of specimens, recording in a laboratory register, smear preparation, staining procedures, microscope examination, reporting and recording, and quality control in the TB laboratory. A quiz is included to measure what was learned from the video and other training materials.

•

Cardiopulmonary Disease and Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 1997. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: Available as part of a package of 21 different lupusrelated brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus discusses cardiopulmonary involvement in systemic lupus erythematosus (SLE). Lupus may cause inflammation of the pericardium, the myocardium, and the endocardium, as well as narrowing of the coronary arteries. The pamphlet discusses the symptoms of and treatment for pericarditis and myocarditis, and it highlights the features of endocarditis and coronary artery disease. The pamphlet describes the pulmonary manifestations of SLE, including pleuritis, pneumonitis, chronic diffuse interstitial lung disease, and pulmonary hypertension. It notes the modes of treating these pulmonary manifestations. The pamphlet stresses that early and accurate diagnosis of problems and aggressive

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treatment to reduce organ damage are critical to the successful management of cardiopulmonary disease in lupus. It concludes with information on the Lupus Foundation of America. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “lung disease” (or synonyms). The following was recently posted: •

Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants Source: American Academy of Pediatrics - Medical Specialty Society; 2002 February; 9 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3175&nbr=2401&a mp;string=lung+AND+disease Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

American Indians/Alaskan Natives and Lung Disease Summary: This fact sheet provides statistics on lung disease within the American Indian/Alaska Native population. Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6831

•

Bloom Syndrome Summary: Basic patient education information about blooms syndrome. Children with this genetic disorder are prone to cancer, chronic lung disease, and diabetes. Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4513

•

Fact Sheet: Asian Americans/Pacific Islanders and Lung Disease Summary: A fact sheet on lung disease in Asian Americans and Pacific Islanders. Source: CDC National Prevention Information Network http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7258

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Facts About Lymphangioleiomyomatosis (LAM) Summary: This fact sheet contains basic consumer health education information about this a rare lung disease that is characterized by an unusual type of muscle cell that invades the tissue of the lungs, Source: National Heart, Lung, and Blood Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2616

•

Interstitial Lung Disease (ILD) Summary: This web site links users to basic information and related resources for interstitial lung disease -- a category of lung diseases that includes more than 130 disorders and is characterized by scarring Source: National Jewish Medical and Research Center http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2289

•

Occupational Lung Disease Summary: Information about a variety of occupational lung and respiratory diseases, including brown lung, silicosis, asbestosis and occupational lung cancer. Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4171

•

Preventing Silicosis Summary: This fact sheet discusses this disabling, nonreversible and sometimes fatal lung disease caused by overexposure to respirable crystalline silica. Source: National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2958

•

Work-Related Lung Disease Surveillance Report Summary: The fourth in a series of occupational respiratory disease surveillance reports produced by the National Institute for Occupational Safety and Health (NIOSH). Source: National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4172 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to lung disease. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals

212 Lung Disease

and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lung disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lung disease. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about lung disease. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/.

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Simply type in “lung disease” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “lung disease”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “lung disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “lung disease” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on lung disease: •

Basic Guidelines for Lung Disease Lung disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000066.htm Lung disease - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002158.htm

•

Signs & Symptoms for Lung Disease Lung disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000066.htm

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Diagnostics and Tests for Lung Disease Lung function Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003443.htm

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Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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LUNG DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenopathy: Large or swollen lymph glands. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH]

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Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or

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manifestations of a disease appear in an individual. [NIH] Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Pollutants: Substances which pollute the air. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Albinism: General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha

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1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU]

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Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Anhydrides: Chemical compounds derived from acids by the elimination of a molecule of water. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Annexins: Family of calcium- and phospholipid-binding proteins which are structurally related and exhibit immunological cross-reactivity. Each member contains four homologous 70 kD repeats. The annexins are differentially distributed in vertebrate tissues (and lower eukaryotes) and appear to be involved in membrane fusion and signal transduction. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another

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living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antituberculosis: Refers to a drug used to treat tuberculosis. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU]

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Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the

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intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arthralgia: Pain in the joint. [NIH] Artificial Eye: Usually made of artificial plastic material or glass to which small quantities of metallic oxides have been added in order to imitate the features and coloring of the various parts of t he human eye; a prosthesis made of glass, plastic, or similar material. [NIH] Artificial Limbs: Prosthetic replacements for arms, legs, and parts therof. [NIH] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Asbestos: Fibrous incombustible mineral composed of magnesium and calcium silicates with or without other elements. It is relatively inert chemically and used in thermal insulation and fireproofing. Inhalation of dust causes asbestosis and later lung and gastrointestinal neoplasms. [NIH] Asbestosis: A lung disorder caused by constant inhalation of asbestos particles. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atelectasis: Incomplete expansion of the lung. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU]

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Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Azotemia: An excess of urea or other nitrogenous compounds in the blood. [EU] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Barotrauma: Injury following pressure changes; includes injury to the eustachian tube, ear drum, lung and stomach. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components

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such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Berylliosis: A lung disease caused by exposure to metallic beryllium or its soluble salts. [NIH]

Beryllium: An element with the atomic symbol Be, atomic number 4, and atomic weight 9.01218. Short exposure to this element can lead to a type of poisoning known as berylliosis. [NIH]

Beta 2-Microglobulin: An 11 kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH]

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Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomedical Engineering: Application of principles and practices of engineering science to biomedical research and health care. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH]

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Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy

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on the interstitial lung tissue. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Bronchoscope: A thin, lighted tube used to examine the inside of the trachea and bronchi, the air passages that lead into the lungs. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Compounds: Inorganic compounds that contain cadmium as an integral part of the molecule. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Cannula: A tube for insertion into a duct or cavity; during insertion its lumen is usually occupied by a trocar. [EU] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capnography: Continuous recording of the carbon dioxide content of expired air. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU]

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Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiac catheterization: A procedure in which a thin, hollow tube is inserted into a blood vessel. The tube is then advanced through the vessel into the heart, enabling a physician to study the heart and its pumping activity. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalyse: To speed up a chemical reaction. [EU] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DCshock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject

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or remove liquids. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH]

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Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH]

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Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agents: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of acetylcholine, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of muscarinic agonists, although most modern texts discourage that usage. [NIH] Chorioamnionitis: An inflammatory process involving the chorion, its fetal blood vessels, the umbilical cord, and the amnion by extension of the inflammation, as the amnion itself has no blood supply. This inflammatory process is potentially fatal to mother and fetus. [NIH]

Chorion: The outermost extraembryonic membrane. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Claudication: Limping or lameness. [EU] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other

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medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire

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functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH]

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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consolidation: The healing process of a bone fracture. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a

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myocardial infarction. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryoglobulinemia: A condition characterized by the presence of abnormal or abnormal quantities of cryoglobulins in the blood. They are precipitated into the microvasculature on exposure to cold and cause restricted blood flow in exposed areas. [NIH] CSF: Cerebrospinal fluid. The fluid flowing around the brain and spinal cord. CSF is produced in the ventricles of the brain. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical

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compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]

Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [NIH] Cytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytophaga: A genus of gram-negative gliding bacteria found in soil, decomposing organic matter, and freshwater and marine habitats. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoplasmic Granules: Condensed areas of cellular material that may be bounded by a membrane. [NIH] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Deception: The act of deceiving or the fact or condition of being deceived. [NIH]

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Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desmosine: 4-(4-Amino-4-carboxybutyl)-1-(5-amino-5-carboxypentyl)-3,5-bis(3-amino-3carboxypropyl)pyridinium. A rare amino acid found in elastin, formed by condensation of four molecules of lysine into a pyridinium ring. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic Imaging: Any visual display of structural or functional patterns of organs or tissues for diagnostic evaluation. It includes measuring physiologic and metabolic responses to physical and chemical stimuli, as well as ultramicroscopy. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are

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the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended

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effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Drug Toxicity: Manifestations of the adverse effects of drugs administered therapeutically or in the course of diagnostic techniques. It does not include accidental or intentional poisoning for which specific headings are available. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphagia: Difficulty in swallowing. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dyspnoea: Difficult or laboured breathing. [EU] Echinococcosis: An infection caused by the infestation of the larval form of tapeworms of the genus Echinococcus. The liver, lungs, and kidney are the most common areas of infestation. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The

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numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] Endotracheal intubation: Insertion of an airtube into the windpipe. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small

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intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidemiology, Molecular: The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH]

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Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Atresia: Congenital failure of the full esophageal lumen to develop that commonly occurs with tracheoesophageal fistula. Symptoms include excessive salivation, gagging, cyanosis, and dyspnea. [NIH] Esophageal Stricture: A narrowing of the esophagus often caused by acid flowing back from the stomach. This condition may require surgery. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by

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determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]

Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH]

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Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial arrhythmias and tachycardias. Paradoxically, however, in myocardial infarct patients with either symptomatic or asymptomatic arrhythmia, flecainide exacerbates the arrhythmia and is not recommended for use in these patients. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH]

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Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forced Expiratory Volume: Measure of the maximum amount of air during a forced vital capacity determination that can be expelled in a given number of seconds. It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the

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esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Neoplasms: Tumors or cancer of the gastrointestinal system. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestation period: The period of development of the young from the time of conception until birth. [NIH] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliding Bacteria: Bacteria having the ability to move upon a solid surface without any visible means of locomotion. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with

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leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of health-

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related institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hantavirus: A genus of the family Bunyaviridae causing Hantavirus infections, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. The genus has one recognized group (Hantaan group) consisting of several species including Dobrava-Belgrade virus, Seoul virus, Prospect Hill virus, Puumala virus, Thottapalayam virus, and Hantaan virus, the type species. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary

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disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH]

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Hepatocyte Growth Factor: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is proto-oncogene protein C-met. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the opening. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hospice: Institution dedicated to caring for the terminally ill. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or

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bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol

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and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hyperstimulation: Excessive stimulation. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH]

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Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]

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Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhalation Exposure: The exposure to potentially harmful chemical, physical, or biological agents by inhaling them. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own

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psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukin-9: Factor that is thought to be a regulator of hematopoiesis. It has been shown to enhance the growth of human mast cells and megakaryoblastic leukemic cells as well as murine helper t-cell clones. IL-9 is a glycoprotein with a molecular weight of 32-39 that is derived from T-cells, and maps to human chromosome 5. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of

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diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation;

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those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isocyanates: Organic compounds that contain the -NCO radical. [NIH] Isodesmosine: 2-(4-Amino-4-carboxybutyl)-1-(5-amino-5-carboxypentyl)-3,5-bis(3-amino-3carboxypropyl)pyridinium. A rare amino acid found in elastin, formed by condensation of four molecules of lysine into a pyridinium ring. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared

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differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Legionellosis: Infections with bacteria of the genus Legionella. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukocyte Disorders: Disordered formation of various types of leukocytes or an abnormal accumulation or deficiency of these cells. [NIH] Leukocyte Elastase: An enzyme that catalyzes the hydrolysis of proteins, including elastin. It cleaves preferentially bonds at the carboxyl side of Ala and Val, with greater specificity for Ala. EC 3.4.21.37. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH]

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Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Living will: A health care directive that tells others how a person would like to be treated if they lose their capacity to make decisions about health care; it contains instructions about the person's choices of medical treatment and it is prepared in advance. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair. It is detected when heterozygous markers for a locus appear monomorphic because one of the alleles was

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deleted. When this occurs at a tumor suppressor gene locus where one of the alleles is already abnormal, it can result in neoplastic transformation. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lung volume: The amount of air the lungs hold. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an

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animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Mechanoreceptors: Cells specialized to transduce mechanical stimuli and relay that information centrally in the nervous system. Mechanoreceptors include hair cells, which mediate hearing and balance, and the various somatosensory receptors, often with nonneural accessory structures. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning,

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(2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meniscus: A fibro-cartilage within a joint, especially of the knee. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Health Services: Organized services to provide mental health care. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through

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this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Mode of Transmission: Hepatitis A [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Monogenic: A human disease caused by a mutation in a single gene. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH]

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Motility: The ability to move spontaneously. [EU] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucociliary Clearance: Rate of ciliary and secretory activity of the respiratory submucosal glands. It is a non-specific host defense mechanism, measurable in vivo by mucus transfer, ciliary beat frequency, and clearance of radioactive tracers. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (receptors, muscarinic). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU]

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Myositis: Inflammation of a voluntary muscle. [EU] Naphthols: Naphthalene derivatives carrying one or more hydroxyl (-OH) groups at any ring position. They are often used in dyes and pigments, as antioxidants for rubber, fats, and oils, as insecticides, in pharmaceuticals, and in numerous other applications. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Polyps: Focal accumulations of edema fluid in the nasal mucosa accompanied by hyperplasia of the associated submucosal connective tissue. Polyps may be neoplasms, foci of inflammation, degenerative lesions, or malformations. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nebulizer: A device used to turn liquid into a fine spray. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatology: A subspecialty of pediatrics concerned with the newborn infant. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH]

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Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Dioxide: Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]

Nonmalignant: Not cancerous. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a

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widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Medicine: A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds in a pharmaceutical form. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH]

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Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate

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and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic enzymes: A group of proteins secreted by the pancreas which aid in the digestion of food. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH]

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Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]

Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation

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and ending 7 to 28 days after birth. [EU] Periodontal Attachment Loss: Loss or destruction of periodontal tissue caused by periodontitis or other destructive periodontal diseases or by injury during instrumentation. Attachment refers to the periodontal ligament which attaches to the alveolar bone. It has been hypothesized that treatment of the underlying periodontal disease and the seeding of periodontal ligament cells enable the creating of new attachment. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal Ligament: Fibrous connective tissue surrounding the root of a tooth that separates it from and attaches it to the alveolar bone. [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Perivascular: Situated around a vessel. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not

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stored in large amounts in the system. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH]

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Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]

Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH]

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Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH]

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Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Programmed Instruction: Instruction in which learners progress at their own rate using workbooks, textbooks, or electromechanical devices that provide information in discrete steps, test learning at each step, and provide immediate feedback about achievement. (ERIC, Thesaurus of ERIC Descriptors, 1996). [NIH]

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Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prokinetic Drugs: Medicines that cause muscles in the GI tract to move food. An example is cisapride (SIS-uh-pryd) (Propulsid). [NIH] Prolapse: The protrusion of an organ or part of an organ into a natural or artificial orifice. [NIH]

Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH]

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Prostheses and Implants: Artificial substitutes for body parts, and materials inserted into tissue for functional, cosmetic, or therapeutic purposes. Prostheses can be functional, as in the case of artificial arms and legs, or cosmetic, as in the case of an artificial eye. Implants, all surgically inserted or grafted into the body, tend to be used therapeutically. Experimental implants is available for those used experimentally. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH]

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Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary Gas Exchange: The exchange of oxygen and carbon dioxide between alveolar air and pulmonary capillary blood. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH]

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Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiologist: A doctor who specializes in creating and interpreting pictures of areas inside the body. The pictures are produced with x-rays, sound waves, or other types of energy. [NIH]

Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [NIH]

Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers. [NIH] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU]

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Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Registries: The systems and processes involved in the establishment, support, management, and operation of registers, e.g., disease registers. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH]

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Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respirable: Dust particles smaller than 0. 005 mm, which are deposited in the respiratory region of the lungs. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Mechanics: The physical or mechanical action of the lungs, diaphragm, ribs, and chest wall during respiration. It includes airflow, lung volume, neural and reflex controls, mechanoreceptors, breathing patterns, etc. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Respiratory Therapy: Care of patients with deficiencies and abnormalities associated with the cardiopulmonary system. It includes the therapeutic use of medical gases and their administrative apparatus, environmental control systems, humidification, aerosols, ventilatory support, bronchopulmonary drainage and exercise, respiratory rehabilitation, assistance with cardiopulmonary resuscitation, and maintenance of natural, artificial, and mechanical airways. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH]

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Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH]

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Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of

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old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicosis: A type of pneumoconiosis caused by inhalation of particles of silica, quartz, ganister or slate. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport

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mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmogenic: Capable of producing convulsions. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specific immune cells: Immune cells such as T and B lymphocytes that respond to a single, specific antigen. [NIH]

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Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Stenosis: Narrowing of the spinal canal. [NIH] Spirochete: Lyme disease. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group. [NIH]

Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

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Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptomyces: A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the antibiotics of practical value. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Subtilisin: A serine endopeptidase isolated from Bacillus subtilis. It hydrolyzes proteins with broad specificity for peptide bonds, and a preference for a large uncharged residue in P1. It also hydrolyzes peptide amides. (From Enzyme Nomenclature, 1992) EC 3.4.21.62. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of

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pus. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Survival Analysis: A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systems Analysis: The analysis of an activity, procedure, method, technique, or business to determine what must be accomplished and how the necessary operations may best be accomplished. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH]

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Telecommunications: Transmission of information over distances via electronic means. [NIH]

Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU]

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Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroiditis, Autoimmune: Progressive enlargement of the thyroid gland, often associated with hypothyroidism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheoesophageal Fistula: Abnormal communication between the esophagus and the trachea, acquired or congenital, often associated with esophageal atresia. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

Transcription Factors: Endogenous substances, usually proteins, which are effective in the

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initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body.

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Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Uridine Triphosphate: Uridine 5'-(tetrahydrogen triphosphate). A uracil nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in

302 Lung Disease

the bladder, and leaves the body through the urethra. [NIH] Urine Testing: Checking urine to see if it contains glucose (sugar) and ketones. Special strips of paper or tablets (called reagents) are put into a small amount of urine or urine plus water. Changes in the color of the strip show the amount of glucose or ketones in the urine. Urine testing is the only way to check for the presence of ketones, a sign of serious illness. However, urine testing is less desirable then blood testing for monitoring the level of glucose in the body. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of

Dictionary 303

one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vital Capacity: The volume of air that is exhaled by a maximal expiration following a maximal inspiration. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

304 Lung Disease

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

305

INDEX A Abdomen, 223, 234, 238, 265, 268, 295, 296, 298, 303 Abdominal, 176, 223, 246, 266, 278 Aberrant, 32, 57, 58, 223 Ablate, 223, 236, 248 Abscess, 176, 223 Acceptor, 223, 268, 277, 299 Acetylcholine, 44, 223, 239, 275 Activities of Daily Living, 132, 223 Acute renal, 177, 223 Adaptability, 223, 237 Adaptation, 223, 264 Adenine, 159, 223, 224, 287 Adenocarcinoma, 6, 223 Adenopathy, 177, 223 Adenosine, 11, 142, 159, 223, 224, 235, 281 Adenosine Deaminase, 11, 223 Adenosine Triphosphate, 142, 224, 281 Adenovirus, 59, 224 Adhesions, 151, 224 Adipose Tissue, 224, 278 Adjuvant, 145, 224 Adoptive Transfer, 37, 60, 224 Adrenal Cortex, 224, 243, 260, 284 Adrenal Glands, 224 Adrenal insufficiency, 47, 224 Adrenergic, 153, 190, 224, 247, 250 Adrenergic Agonists, 153, 224 Adsorption, 56, 224 Adsorptive, 224 Adverse Effect, 36, 39, 47, 153, 224, 248, 293 Aerobic, 118, 160, 224, 251, 277, 287 Aerosol, 21, 38, 39, 143, 164, 224, 275 Affinity, 224, 225, 294 Age of Onset, 224, 234, 301 Age-Adjusted, 152, 225 Agonist, 56, 159, 225, 247, 275 Air Pollutants, 29, 225 Air Sacs, 155, 225, 226 Airway Obstruction, 17, 65, 157, 225 Albinism, 208, 209, 225 Albumin, 7, 225, 277, 281 Aldehydes, 132, 225 Alertness, 225, 235 Algorithms, 32, 225, 233 Alimentary, 225, 249

Alkaline, 225, 226, 235 Alkaloid, 225, 240, 272, 275 Alleles, 25, 28, 30, 62, 69, 225, 268 Allergen, 19, 41, 225, 293 Allergic Rhinitis, 152, 225 Allogeneic, 68, 225, 257 Allograft, 65, 225 Alopecia, 225, 244 Alpha 1-Antitrypsin, 13, 64, 125, 207, 225 Alpha-1, 49, 84, 226 Alpha-Defensins, 61, 226, 245 Alternative medicine, 186, 226 Alternative Splicing, 226, 286 Alum, 17, 226 Aluminum, 226 Alveoli, 10, 31, 153, 155, 160, 162, 187, 226, 302 Alveolitis, 156, 176, 226 Ameliorating, 48, 226 Amino Acid Sequence, 150, 226, 228, 252, 255 Amino Acids, 56, 143, 226, 251, 255, 279, 283, 286, 291, 293, 296, 300, 301 Ammonia, 132, 223, 226, 297, 301 Amnion, 226, 239 Amniotic Fluid, 226, 255 Anaesthesia, 94, 226, 263 Anal, 226, 250, 253 Analgesic, 138, 226, 272, 275, 276 Analog, 141, 227 Analogous, 227, 282, 300 Analytes, 202, 227 Anaphylatoxins, 20, 41, 227, 241 Anatomical, 34, 156, 227, 231, 242, 249, 262, 278, 292 Androgens, 224, 227, 243 Anemia, 177, 208, 227, 235 Anergy, 178, 227 Anesthesia, 55, 88, 176, 181, 225, 227, 284 Anesthetics, 55, 227, 231, 250 Angiogenesis, 66, 107, 227, 270 Angiotensin converting enzyme inhibitor, 187, 227 Anhydrides, 132, 227 Animal model, 11, 12, 17, 22, 23, 25, 26, 35, 37, 38, 39, 41, 45, 57, 227 Anions, 225, 227, 265, 284 Annealing, 227, 283

306 Lung Disease

Annexins, 143, 227 Antagonism, 227, 235 Antiallergic, 228, 243 Antibacterial, 228, 284, 295 Antibiotic, 151, 228, 239, 251, 279, 295 Antibodies, 9, 16, 31, 59, 62, 149, 161, 162, 228, 231, 260, 261, 262, 269, 281 Anticoagulant, 228, 286, 303 Antigen-Antibody Complex, 228, 241 Antigen-presenting cell, 60, 228 Anti-infective, 228, 260 Anti-inflammatory, 30, 35, 41, 59, 114, 151, 228, 230, 243, 246, 256, 284 Anti-Inflammatory Agents, 228, 230, 243 Antimicrobial, 32, 91, 228, 245 Antineoplastic, 228, 233, 243, 244, 260 Antioxidant, 16, 35, 54, 57, 228, 277 Antipruritic, 138, 228 Antipyretic, 138, 228 Antithrombotic, 147, 228 Antituberculosis, 87, 228 Antiviral, 169, 228, 279 Anus, 226, 229, 230, 234 Anxiety, 88, 229, 278 Anxiety Disorders, 229, 278 Aorta, 229, 242, 303 Apnea, 149, 229 Apolipoproteins, 229, 268 Apoptosis, 13, 16, 40, 54, 60, 76, 229 Applicability, 128, 229 Aqueous, 229, 231, 244, 260, 267 Arachidonate 12-Lipoxygenase, 229, 268 Arachidonate 15-Lipoxygenase, 229, 268 Arachidonate Lipoxygenases, 229, 268 Arachidonic Acid, 25, 42, 229, 248, 267, 268, 285 Arginine, 17, 48, 227, 229, 275, 300 Aromatic, 138, 229, 280 Arrhythmia, 229, 253 Arterial, 55, 65, 70, 138, 177, 229, 230, 234, 238, 239, 261, 265, 286, 297 Arteries, 56, 188, 209, 229, 230, 233, 238, 242, 269, 271, 273, 287, 298, 301 Arterioles, 229, 230, 233, 235, 271, 302 Arteriosclerosis, 229, 261 Arteriosus, 230, 287 Arteriovenous, 230, 238, 271 Arthralgia, 8, 230 Artificial Eye, 230, 286 Artificial Limbs, 230 Artificial Organs, 145, 230 Asbestos, 13, 27, 151, 230

Asbestosis, 132, 211, 230 Asphyxia, 230, 275 Aspirate, 36, 63, 230 Aspiration, 8, 74, 146, 176, 207, 230 Aspirin, 187, 230 Assay, 7, 21, 38, 73, 141, 230 Astringents, 230, 271 Asymptomatic, 52, 177, 230, 253, 278 Ataxia, 230, 260 Atelectasis, 55, 230 Atopic, 55, 230 Atresia, 175, 230 Atrial, 107, 230, 231, 253, 303 Atrial Fibrillation, 107, 231, 303 Atrium, 230, 231, 303 Atrophy, 7, 8, 231, 275 Attenuated, 231, 247 Attenuation, 20, 231, 288 Atypical, 158, 169, 231 Autoantibodies, 60, 231 Autoantigens, 60, 231 Autodigestion, 231, 278 Autoimmune disease, 83, 142, 177, 231, 273 Autonomic, 223, 231, 276, 280 Azotemia, 7, 231, 301 B Bacterial Infections, 145, 231, 238 Bacterium, 149, 231 Bacteriuria, 231, 301 Barbiturate, 231, 298 Barotrauma, 70, 78, 231 Base, 14, 49, 132, 223, 231, 244, 245, 254, 255, 266, 298, 301 Base Sequence, 231, 254, 255 Basement Membrane, 36, 231, 252, 266 Basophils, 232, 257, 267 Benign, 8, 39, 89, 232, 234, 257, 274 Benign tumor, 39, 232 Benzene, 232 Benzodiazepines, 176, 232 Bereavement, 167, 232 Berylliosis, 232 Beryllium, 23, 34, 53, 71, 74, 114, 203, 232 Beta 2-Microglobulin, 109, 232 Beta-Defensins, 232, 245 Beta-Thromboglobulin, 232, 264 Bile, 232, 254, 260, 268, 295 Bile Acids, 232, 254, 295 Bile Ducts, 232 Biliary, 60, 232, 278 Biliary Tract, 232, 278

Index 307

Bilirubin, 225, 232 Binding Sites, 143, 232 Bioavailable, 105, 233 Biochemical, 16, 17, 24, 42, 46, 47, 50, 62, 122, 225, 226, 233, 234, 253, 298 Biochemical reactions, 233, 298 Bioengineering, 33, 50, 196, 233 Biological therapy, 233, 257 Biological Transport, 233, 246 Biomarkers, 9, 13, 14, 22, 32, 233 Biomedical Engineering, 64, 233 Biopsy, 15, 46, 65, 78, 95, 101, 111, 122, 123, 157, 177, 178, 233 Biosynthesis, 229, 233, 293 Biotechnology, 66, 67, 173, 186, 197, 233 Bladder, 233, 262, 273, 285, 301, 302 Bleomycin, 25, 59, 233 Blood Coagulation, 233, 235, 298 Blood Glucose, 233, 258, 264 Blood pressure, 4, 168, 177, 188, 208, 233, 236, 261, 272, 287, 294 Body Fluids, 233, 248, 253, 276, 294, 300 Body Mass Index, 5, 234, 277 Bone Marrow, 41, 61, 83, 232, 234, 244, 262, 269, 294, 295 Bone scan, 234, 292 Bowel, 226, 234, 246, 250, 263, 265, 296 Bowel Movement, 234, 246, 296 Bradykinin, 234, 275, 281 Brain Ischemia, 234, 238 Brain Neoplasms, 234, 260 Brain Stem, 234, 238 Branch, 119, 120, 179, 202, 219, 234, 279, 287, 294, 298 Breakdown, 234, 246, 254 Breeding, 19, 234 Bronchi, 234, 235, 250, 299 Bronchial, 40, 41, 110, 122, 133, 139, 140, 147, 154, 234, 235, 259 Bronchiectasis, 53, 72, 104, 157, 176, 203, 234 Bronchioles, 152, 153, 160, 226, 234 Bronchitis, 4, 44, 123, 133, 143, 145, 147, 152, 153, 154, 157, 162, 173, 174, 202, 234, 239 Bronchoalveolar Lavage, 23, 32, 54, 61, 80, 110, 122, 123, 125, 177, 234 Bronchoalveolar Lavage Fluid, 80, 234 Bronchodilator, 109, 235 Bronchopulmonary, 17, 19, 43, 59, 72, 73, 95, 120, 121, 125, 126, 129, 130, 160, 204, 235, 290

Bronchopulmonary Dysplasia, 19, 43, 59, 95, 120, 121, 125, 126, 129, 130, 160, 204, 235 Bronchoscope, 160, 235 Bronchoscopy, 51, 61, 121, 202, 235 Buccal, 235, 269 C Cadmium, 20, 235 Cadmium Compounds, 235 Cadmium Poisoning, 20, 235 Caffeine, 208, 235, 287 Calcinosis, 8, 235 Calcium, 8, 35, 56, 105, 143, 146, 187, 227, 230, 235, 241, 260, 270, 286, 292, 293 Caloric intake, 140, 235 Cannula, 138, 139, 235 Capillary, 102, 234, 235, 287, 303 Capnography, 162, 235 Carbohydrate, 146, 235, 243, 256, 283 Carbon Dioxide, 140, 146, 155, 162, 235, 236, 253, 254, 287, 290, 302 Carcinogenic, 232, 236, 263, 285, 295 Carcinogens, 236, 250, 273, 276, 277 Carcinoma, 6, 176, 236, 246 Cardiac, 8, 38, 177, 178, 231, 235, 236, 249, 250, 273, 290, 295 Cardiac catheterization, 236 Cardiopulmonary, 38, 47, 86, 125, 209, 236, 290 Cardiorespiratory, 132, 174, 236 Cardiovascular, 10, 51, 91, 92, 98, 107, 111, 114, 152, 170, 236, 251, 267, 298 Cardiovascular disease, 152, 236 Carnitine, 116, 236 Carrier Proteins, 236, 281 Case report, 106, 236, 240 Case series, 236, 240 Catabolism, 31, 236 Catalyse, 236, 299 Catecholamines, 80, 236, 247 Catheter Ablation, 107, 236 Catheterization, 236, 265 Catheters, 145, 236 Cations, 237, 265 Caudal, 237, 246, 283 Causal, 14, 22, 237, 250 Causality, 88, 237 Cause of Death, 54, 152, 154, 237, 244 Celiac Disease, 6, 237 Cell, 6, 7, 10, 12, 13, 15, 17, 18, 20, 23, 26, 30, 33, 34, 37, 38, 39, 41, 42, 44, 45, 46, 48, 50, 51, 53, 54, 55, 56, 57, 58, 59, 60,

308 Lung Disease

61, 62, 68, 69, 91, 101, 104, 108, 143, 161, 168, 211, 225, 227, 228, 229, 230, 231, 232, 233, 236, 237, 239, 241, 244, 245, 246, 248, 249, 252, 253, 255, 257, 258, 259, 260, 262, 263, 264, 265, 266, 267, 270, 272, 274, 276, 277, 280, 281, 282, 283, 285, 289, 290, 292, 293, 297, 298, 300, 301, 302, 303 Cell Adhesion, 23, 61, 161, 237 Cell Cycle, 13, 237, 244 Cell Death, 229, 237, 255, 274 Cell Differentiation, 59, 237, 293 Cell Division, 231, 237, 257, 272, 281, 292 Cell membrane, 233, 236, 237, 239, 246, 265, 270, 280 Cell motility, 237, 259 Cell Physiology, 10, 104, 237 Cell proliferation, 54, 57, 91, 230, 237, 264, 293 Cell Respiration, 237, 277, 290 Cell Size, 237, 253 Cell Survival, 13, 57, 237, 257 Cell Transplantation, 237 Central Nervous System, 16, 164, 223, 232, 234, 235, 238, 254, 256, 257, 260, 267, 272, 273 Central Nervous System Infections, 238, 257, 260 Ceramide, 40, 238 Cerebellum, 234, 238 Cerebral, 47, 73, 230, 234, 238, 242, 245, 250, 251, 253, 260, 287 Cerebral Infarction, 238, 260 Cerebral Palsy, 47, 238 Cerebrospinal, 238, 243, 260, 293 Cerebrospinal fluid, 238, 243, 260, 293 Cerebrovascular, 5, 177, 236, 238 Cerebrovascular Disorders, 5, 238 Cerebrum, 238, 300 Character, 238, 245, 256 Chemokines, 15, 16, 26, 238 Chemotactic Factors, 238, 241 Chemotherapy, 81, 90, 91, 114, 147, 168, 173, 175, 238 Chest wall, 33, 51, 238, 282, 290 Chimeras, 61, 238 Chloride Channels, 11, 239 Chlorine, 132, 239 Cholesterol, 7, 58, 232, 239, 242, 260, 268, 269, 295 Cholesterol Esters, 239, 268 Cholinergic, 152, 153, 239, 273, 275

Cholinergic Agents, 153, 239 Chorioamnionitis, 73, 109, 239 Chorion, 239 Chromatin, 229, 239 Chromosome, 24, 39, 239, 264, 267, 268, 292 Chronic Disease, 128, 174, 187, 239, 240 Chronic renal, 4, 177, 239, 301 Chylomicrons, 239, 268 Ciliary, 45, 204, 230, 239, 273, 302 Clarithromycin, 107, 239 Claudication, 5, 239 Cleft Palate, 88, 239 Clinical Medicine, 98, 110, 239, 284 Clinical study, 36, 45, 239 Clinical trial, 9, 31, 35, 61, 63, 66, 119, 127, 134, 197, 240, 242, 244, 247, 279, 286, 288 Cloning, 233, 240, 267 Coagulation, 84, 177, 233, 240, 281, 298, 303 Coal, 105, 117, 169, 232, 240 Cofactor, 240, 275, 286, 298 Cohort Studies, 240, 250 Colchicine, 8, 178, 187, 240 Colitis, 240, 263 Collagen, 23, 32, 75, 80, 84, 89, 153, 232, 240, 252, 253, 260, 270, 282, 285 Collagen disease, 240, 260 Collapse, 52, 234, 240, 282, 294 Colloidal, 225, 240 Colorectal, 81, 114, 240 Colorectal Cancer, 81, 114, 240 Complement, 7, 19, 40, 61, 227, 240, 241, 270, 281, 293 Complement Activation, 19, 227, 241 Computational Biology, 197, 241 Computed tomography, 51, 77, 87, 107, 114, 157, 241, 292 Computerized axial tomography, 241, 292 Computerized tomography, 241 Conception, 241, 253, 255, 295 Concomitant, 5, 36, 157, 241 Conduction, 177, 236, 241 Congestive heart failure, 5, 45, 177, 241 Conjunctiva, 241, 263 Connective Tissue, 23, 32, 176, 234, 240, 242, 253, 254, 269, 271, 274, 280, 291, 297 Connective Tissue Cells, 242 Consciousness, 226, 242, 245, 290 Consolidation, 94, 242 Constitutional, 178, 242 Constriction, 56, 242, 266, 302

Index 309

Constriction, Pathologic, 242, 302 Consultation, 22, 242 Consumption, 175, 242, 276, 277 Continuum, 6, 242 Contraindications, ii, 242 Control group, 128, 242 Conus, 242, 287 Convulsions, 231, 242, 248, 261, 294 Coordination, 238, 242, 273 Cornea, 242, 292, 296, 302 Coronary, 39, 88, 177, 209, 236, 242, 271, 273 Coronary Artery Bypass, 88, 242 Coronary heart disease, 39, 236, 242 Coronary Thrombosis, 242, 271, 273 Cortical, 243, 251, 292 Corticosteroid, 35, 243, 284 Cortisol, 47, 225, 243 Cortisone, 243, 246, 284 Coumarins, 243, 286 Craniocerebral Trauma, 243, 257, 260 Creatine, 104, 243 Creatinine, 243, 301 Cross-Sectional Studies, 243, 250 Cryoglobulinemia, 7, 243 CSF, 21, 31, 232, 238, 243 Curative, 243, 298 Cutaneous, 8, 187, 243, 265, 269 Cyanosis, 243, 251 Cyclic, 235, 243, 257, 275, 285 Cyclin, 13, 244 Cyclin-Dependent Kinases, 13, 244 Cyclophosphamide, 76, 107, 122, 127, 187, 244 Cyclosporine, 8, 106, 178, 244 Cyst, 230, 244 Cysteine, 12, 29, 238, 244, 245, 296 Cystine, 244 Cytidine, 159, 244 Cytidine Diphosphate, 159, 244 Cytokine, 12, 17, 18, 23, 32, 35, 38, 41, 53, 55, 57, 65, 158, 244, 264, 298 Cytophaga, 101, 244 Cytoplasm, 229, 232, 237, 244, 250, 257, 291, 292 Cytoplasmic Granules, 140, 244 Cytosine, 244 Cytotoxic, 61, 244, 262, 293 D Data Collection, 6, 58, 244, 254 Databases, Bibliographic, 197, 244 Death Certificates, 20, 244

Deception, 208, 244 Decision Making, 42, 81, 245 Defense Mechanisms, 42, 63, 245 Defensins, 61, 104, 226, 232, 245 Degenerative, 242, 245, 258, 274 Dehydration, 207, 245 Dehydroepiandrosterone, 152, 245 Deletion, 27, 56, 229, 245, 268 Delirium, 5, 245 Delivery of Health Care, 245, 258 Dementia, 4, 5, 245 Denaturation, 245, 283 Dendrites, 245, 275 Dendritic, 16, 245 Density, 58, 146, 234, 245, 253, 268, 276, 288, 294 Dental Caries, 186, 187, 245 Depersonalization, 246, 278 Depolarization, 56, 246, 293 Derealization, 246, 278 Dermal, 8, 246 Dermatitis, 246, 248 DES, 227, 246 Desmosine, 97, 246 Deuterium, 246, 260 Dexamethasone, 47, 71, 75, 76, 77, 80, 84, 94, 103, 108, 246 Diabetes Mellitus, 4, 147, 177, 246, 256, 258 Diagnostic Imaging, 157, 246 Diagnostic procedure, 137, 186, 246 Diaphragm, 246, 259, 282, 290 Diastolic, 246, 261 Diencephalon, 238, 246 Diffusion, 155, 233, 246, 247, 263, 265, 275 Digestion, 145, 225, 232, 234, 246, 265, 268, 278, 296, 302 Digestive system, 134, 246, 254, 273 Digestive tract, 246, 294 Dilatation, 8, 234, 247, 302 Dilation, 56, 234, 247, 260 Dilution, 51, 247 Direct, iii, 10, 11, 22, 52, 55, 78, 176, 189, 209, 236, 239, 247, 269, 289 Disease Progression, 46, 157, 247 Disorientation, 245, 247 Disparity, 30, 247 Distal, 78, 152, 153, 236, 242, 247, 254, 287 Diuresis, 235, 247 Dizziness, 247, 278 Domesticated, 247, 257 Dopamine, 247, 280

310 Lung Disease

Dorsal, 247, 283 Double-blinded, 57, 247 Drive, ii, vi, 6, 113, 147, 175, 177, 187, 209, 247, 265 Drug Interactions, 191, 247 Drug Resistance, 87, 168, 247 Drug Tolerance, 247, 299 Drug Toxicity, 7, 248 Duct, 235, 236, 248, 252, 291, 297 Duodenum, 232, 248, 254, 278, 296 Dyes, 232, 248, 254, 274 Dyskinesia, 45, 204, 248 Dysphagia, 8, 207, 248 Dysplasia, 17, 72, 73, 160, 248 Dyspnea, 8, 79, 97, 103, 128, 133, 157, 248, 251, 278, 287 Dyspnoea, 101, 248 E Echinococcosis, 90, 248 Eczema, 77, 248 Edema, 7, 248, 265, 273, 274, 275, 301 Effector, 17, 55, 223, 241, 248 Effector cell, 55, 248 Efficacy, 11, 18, 48, 92, 122, 126, 131, 248, 300 Eicosanoids, 25, 248 Elastin, 140, 153, 240, 246, 248, 252, 266, 267 Elective, 9, 248 Electrocoagulation, 240, 248 Electroconvulsive Therapy, 5, 248 Electrolyte, 243, 245, 248, 253, 272, 276, 294, 301 Electrons, 228, 231, 248, 265, 277, 288 Emboli, 46, 249, 265, 303 Embolism, 249, 265, 287, 303 Embolization, 46, 249, 303 Embryo, 226, 237, 249, 263, 282, 301 Enamel, 245, 249 Endemic, 249, 295 Endocarditis, 209, 249 Endocardium, 209, 249 Endocrine System, 249, 275 Endocytosis, 44, 249 Endoscopy, 8, 175, 249 Endothelial cell, 60, 61, 102, 249, 264, 298 Endothelium, 249, 275, 281 Endothelium-derived, 249, 275 Endotoxin, 12, 18, 59, 63, 101, 249, 301 Endotracheal intubation, 146, 249 End-stage renal, 239, 249 Enteral Nutrition, 128, 249

Enteritis, 6, 249 Enterocolitis, 250 Enteropeptidase, 250, 300 Environmental Exposure, 29, 70, 250, 276 Environmental Health, 21, 29, 38, 81, 196, 198, 250 Enzymatic, 25, 235, 241, 244, 245, 250, 259, 283, 290 Enzyme Inhibitors, 250, 281 Eosinophil, 158, 250 Eosinophilia, 57, 250 Eosinophilic, 81, 94, 114, 250 Epidemic, 131, 250, 295 Epidemiologic Studies, 38, 57, 132, 250 Epidemiological, 39, 53, 65, 110, 131, 174, 250 Epidemiology, Molecular, 42, 250 Epidermal, 8, 250, 266 Epidermis, 250, 266 Epidural, 88, 250, 265 Epinephrine, 224, 247, 250, 275, 301 Epithelial Cells, 17, 18, 27, 31, 35, 37, 40, 56, 62, 142, 144, 232, 250, 251, 259, 266 Epithelium, 17, 18, 26, 30, 40, 41, 142, 231, 249, 251 Epitope, 59, 251 Erythrocytes, 160, 227, 234, 251, 289, 293 Erythromycin, 239, 251 Esophageal, 8, 175, 207, 251, 255, 299 Esophageal Atresia, 175, 251, 299 Esophageal Stricture, 8, 251 Esophageal Varices, 8, 251 Esophagitis, 8, 175, 251, 255 Esophagus, 6, 8, 175, 230, 246, 247, 251, 254, 255, 258, 269, 280, 289, 296, 298, 299 Ethnic Groups, 152, 177, 251 Eukaryotic Cells, 251, 262 Eustachian tube, 231, 251 Evacuation, 251, 254 Evoke, 251, 296 Excitation, 251, 253 Excitatory, 251, 256 Exercise Test, 47, 121, 251, 252 Exercise Tolerance, 80, 252 Exocrine, 252, 278 Exogenous, 17, 19, 36, 37, 46, 58, 151, 224, 248, 252, 301 Exon, 56, 226, 252 Expiration, 154, 252, 290, 303 Expiratory, 51, 125, 252 Extensor, 252, 287

Index 311

Extracellular, 35, 142, 242, 249, 252, 253, 270, 294 Extracellular Matrix, 35, 242, 252, 253, 270 Extracellular Matrix Proteins, 35, 252, 270 Extracellular Space, 252 Extravasation, 252, 258 Eye Infections, 224, 252 F Family Planning, 168, 197, 252 Fasciculation, 252, 275 Fat, 39, 146, 224, 229, 234, 238, 242, 243, 249, 252, 268, 273, 277, 291, 294, 297, 300 Fatigue, 157, 252, 258 Fatty acids, 225, 248, 252, 256, 268, 285, 298 Fetal Blood, 239, 252 Fetus, 19, 146, 239, 252, 253, 284, 301, 302 Fibrin, 80, 233, 253, 281, 298 Fibrinogen, 253, 281, 286, 298 Fibroblasts, 13, 15, 25, 32, 242, 253, 264 Fibronectin, 23, 253 Fissure, 239, 253 Fixation, 253, 293 Flatus, 253, 254 Flecainide, 77, 253 Flow Cytometry, 13, 253 Fluid Therapy, 253, 276 Fluorescence, 56, 253, 254 Fluorescent Dyes, 253, 254 Focus Groups, 64, 254 Fold, 43, 140, 158, 253, 254 Forced Expiratory Volume, 27, 58, 125, 254 Forearm, 233, 254 Frameshift, 25, 254 Fungi, 17, 187, 252, 254, 271, 272, 304 G Gait, 5, 254 Gallbladder, 223, 232, 246, 254 Ganglia, 223, 230, 234, 254, 273, 274, 280 Gas exchange, 36, 84, 145, 146, 160, 254, 290, 302 Gastric, 8, 175, 176, 231, 236, 254, 258, 259, 260, 288 Gastric Emptying, 8, 175, 254 Gastrin, 254, 259 Gastroenterology, 4, 6, 91, 175, 254 Gastroesophageal Reflux, 8, 254 Gastroesophageal Reflux Disease, 8, 254 Gastrointestinal, 5, 8, 187, 230, 234, 235, 249, 250, 255, 267, 288, 296, 301 Gastrointestinal Neoplasms, 230, 255

Gastrointestinal tract, 5, 187, 255, 267, 301 Gastrostomy, 249, 255 Gene Expression, 32, 46, 54, 57, 59, 255 Genetic Code, 255, 276 Genetic Markers, 120, 255 Genetic testing, 255, 283 Genetics, 29, 42, 44, 45, 50, 85, 110, 120, 122, 129, 223, 255 Genotype, 13, 24, 27, 29, 33, 39, 62, 255, 280 Gestation, 94, 255, 279 Gestation period, 94, 255 Gestational, 19, 36, 105, 255 Gestational Age, 19, 36, 105, 255 Giant Cells, 255, 291 Gland, 52, 224, 243, 255, 269, 278, 279, 281, 285, 292, 296, 297, 299 Gliding Bacteria, 244, 255 Glomerular, 255, 289 Glomeruli, 255, 256 Glomerulonephritis, 7, 255 Glomerulus, 255, 256, 274 Glucocorticoid, 69, 246, 256, 260, 284 Glucose, 4, 87, 233, 246, 256, 258, 261, 263, 264, 288, 291, 302 Glucose Intolerance, 246, 256 Glucuronic Acid, 256, 258 Glutamate, 256 Glutamic Acid, 34, 256, 285 Glutathione Peroxidase, 256, 292 Gluten, 6, 237, 256 Glycerol, 256, 280 Glycerophospholipids, 256, 280 Glycine, 256, 293 Glycoprotein, 93, 142, 225, 253, 255, 256, 257, 264, 266, 273, 298, 301 Glycosaminoglycans, 252, 256 Gonadal, 256, 295 Gout, 240, 256 Governing Board, 256, 283 Gp120, 257, 279 Grade, 6, 257 Graft, 30, 86, 88, 151, 176, 257, 259, 262 Graft Rejection, 151, 257, 262 Grafting, 242, 257 Gram-negative, 32, 244, 257, 287 Granulocytes, 257, 267, 293, 303 Granuloma, 23, 38, 53, 257 Gravidity, 257, 278 Growth factors, 25, 26, 32, 46, 54, 257 Guanylate Cyclase, 257, 275 Guinea Pigs, 38, 41, 257

312 Lung Disease

H Half-Life, 150, 257 Hantavirus, 203, 257 Haplotypes, 28, 30, 257 Headache, 235, 257, 260, 261, 263 Health Care Costs, 47, 152, 258 Health Education, 168, 202, 205, 211, 258 Health Expenditures, 258 Health Status, 4, 258 Heart attack, 208, 236, 258 Heart failure, 4, 5, 258, 287 Heartburn, 258, 259 Hematogenous, 38, 258 Hematoma, 5, 258 Hematopoiesis, 258, 264 Hematuria, 7, 258 Heme, 26, 43, 232, 258, 277 Hemodynamics, 258 Hemoglobin, 160, 227, 243, 251, 258 Hemorrhage, 36, 187, 243, 248, 257, 258, 296 Heparin, 44, 258, 282 Hepatic, 4, 94, 164, 225, 245, 258 Hepatitis, 4, 207, 258, 272 Hepatocyte, 95, 258, 259 Hepatocyte Growth Factor, 95, 259 Hereditary, 49, 226, 256, 259, 290 Heredity, 208, 255, 259 Hernia, 175, 259 Heterogeneity, 27, 28, 62, 224, 259 Heterotrophic, 254, 259 Hiatal Hernia, 175, 259 Histamine, 227, 259, 288 Histamine Release, 227, 259 Histocompatibility, 30, 259 Histology, 8, 259 Holidays, 164, 259 Homeostasis, 12, 31, 259 Homodimer, 259, 300 Homogeneous, 147, 242, 259 Homologous, 225, 227, 259, 292, 293, 297 Hormonal, 231, 243, 259 Hormone, 140, 243, 246, 248, 250, 254, 259, 264, 270, 284, 289, 291, 293, 299, 300 Hospice, 90, 167, 259 Host, 9, 12, 22, 30, 32, 37, 41, 42, 45, 52, 62, 104, 158, 245, 259, 262, 267, 273, 303 Humoral, 12, 38, 55, 257, 259 Humour, 259 Hybridomas, 260, 264 Hydration, 159, 260 Hydrocephalus, 5, 260, 265

Hydrochloric Acid, 132, 260 Hydrocortisone, 47, 260 Hydrogen, 40, 223, 231, 235, 245, 246, 252, 256, 260, 268, 272, 277, 280, 286, 298 Hydrogen Peroxide, 40, 256, 260, 268 Hydrolysis, 223, 260, 265, 267, 280, 283, 286, 300 Hydrophobic, 56, 58, 59, 256, 260, 268 Hydroxylysine, 240, 260 Hydroxyproline, 240, 260 Hydroxyurea, 48, 260 Hygienic, 175, 260 Hypercalcemia, 164, 178, 260 Hypercholesterolemia, 128, 260 Hyperlipidemia, 164, 260 Hyperlipoproteinemia, 260, 261 Hyperoxia, 16, 26, 261 Hyperplasia, 48, 261, 274 Hypersecretion, 20, 261 Hypersensitivity, 23, 38, 53, 88, 151, 152, 225, 250, 261, 267, 291, 293 Hyperstimulation, 18, 261 Hypertension, 5, 48, 51, 118, 128, 147, 177, 236, 261, 265, 301 Hypertriglyceridemia, 164, 261 Hypertrophy, 172, 261 Hypnotic, 231, 261, 298 Hypoglycaemia, 245, 261 Hypotension, 4, 242, 261 Hypothyroidism, 261, 299 Hypoxemia, 4, 55, 261 Hypoxia, 26, 56, 79, 88, 139, 187, 234, 238, 245, 261 I Id, 115, 203, 204, 210, 212, 218, 220, 261 Idiopathic, 7, 11, 21, 23, 25, 31, 37, 46, 49, 127, 129, 261, 291 Imidazole, 259, 261, 288 Immune adjuvant, 226, 261 Immune function, 261, 262, 300 Immune Sera, 261, 262 Immune system, 17, 18, 145, 158, 187, 228, 233, 248, 261, 262, 267, 269, 273, 280, 302, 303 Immunity, 12, 18, 32, 41, 55, 145, 245, 262, 300 Immunization, 149, 224, 262, 293 Immunocompromised, 77, 177, 262 Immunodeficiency, 167, 168, 170, 262 Immunofluorescence, 78, 262 Immunoglobulin, 91, 228, 262, 272 Immunohistochemistry, 21, 50, 262

Index 313

Immunologic, 11, 132, 224, 238, 255, 262 Immunology, 30, 51, 55, 77, 82, 84, 101, 170, 224, 254, 262 Immunosuppressive, 17, 38, 187, 244, 256, 262 Immunosuppressive Agents, 38, 262 Immunosuppressive therapy, 262 Immunotherapy, 16, 224, 233, 262 Impairment, 37, 175, 230, 238, 245, 248, 252, 262, 271, 284 In situ, 50, 177, 262 In Situ Hybridization, 50, 262 In vitro, 17, 21, 23, 27, 32, 38, 53, 57, 58, 59, 61, 63, 262, 283 In vivo, 17, 18, 22, 23, 31, 37, 38, 54, 57, 58, 59, 61, 63, 91, 258, 262, 273, 277, 298 Incision, 262, 265 Incompetence, 254, 262 Incontinence, 6, 260, 262 Indicative, 156, 159, 168, 262, 279, 302 Induction, 17, 26, 40, 55, 150, 227, 263 Infancy, 19, 72, 73, 95, 96, 106, 169, 263 Infant Mortality, 48, 263 Infarction, 234, 238, 263 Infection, 12, 26, 32, 35, 38, 41, 52, 59, 61, 67, 69, 72, 74, 79, 88, 97, 105, 109, 110, 145, 147, 149, 151, 158, 169, 174, 185, 187, 223, 231, 233, 238, 239, 245, 248, 252, 257, 261, 262, 263, 269, 279, 291, 296, 303 Infestation, 248, 263 Infiltration, 8, 26, 158, 256, 263, 284 Inflammatory bowel disease, 151, 209, 263 Influenza, 112, 145, 169, 263 Ingestion, 235, 263, 282 Inhalation Exposure, 22, 263 Initiation, 13, 16, 61, 63, 263, 300 Inorganic, 26, 235, 263, 273, 282 Inositol, 146, 263 Insecticides, 263, 274 Insight, 10, 24, 30, 263 Instillation, 159, 264 Institutionalization, 132, 264 Insulator, 264, 273 Insulin, 46, 94, 105, 264, 301 Insulin-dependent diabetes mellitus, 264 Insulin-like, 46, 105, 264 Intensive Care, 4, 19, 102, 264 Intensive Care Units, 4, 264 Interleukin-1, 161, 264 Interleukin-2, 264 Interleukin-6, 65, 264

Interleukin-8, 63, 65, 264 Interleukin-9, 142, 264 Interleukins, 262, 264 Intermittent, 126, 127, 138, 139, 157, 253, 264, 268 Internal Medicine, 37, 40, 41, 46, 57, 60, 83, 85, 100, 112, 254, 264 Intestinal, 24, 226, 237, 250, 265, 270, 278 Intestine, 234, 240, 249, 265, 266 Intoxication, 245, 265, 304 Intracellular, 56, 58, 59, 235, 263, 265, 270, 275, 285, 292, 293 Intracranial Embolism, 238, 265 Intracranial Embolism and Thrombosis, 238, 265 Intracranial Hemorrhages, 260, 265 Intracranial Hypertension, 257, 260, 265 Intraepithelial, 6, 265 Intramuscular, 149, 265 Intravenous, 8, 93, 107, 127, 187, 190, 265 Intrinsic, 39, 224, 231, 265 Intubation, 236, 265 Invasive, 9, 33, 55, 65, 262, 265, 269 Involuntary, 265, 273, 289, 294 Ion Channels, 11, 161, 265, 297 Ion Transport, 30, 42, 96, 142, 144, 155, 265, 272 Ionizing, 250, 265 Ions, 161, 231, 239, 248, 260, 265, 286, 292 Irritants, 132, 265 Ischemia, 231, 234, 266 Isocyanates, 132, 266 Isodesmosine, 97, 266 J Jejunostomy, 249, 266 Joint, 5, 8, 51, 66, 230, 266, 271, 297 K Kb, 196, 266 Keratinocytes, 264, 266 Keratolytic, 245, 266 Keto, 266, 299 Kidney Disease, 7, 134, 168, 196, 266 Kinetic, 50, 265, 266 L Labile, 240, 266 Laminin, 35, 232, 252, 266 Large Intestine, 240, 246, 247, 265, 266, 289, 294 Larynx, 266, 299 Latency, 38, 266 Latent, 38, 266, 284

314 Lung Disease

Lavage, 33, 66, 72, 73, 75, 83, 114, 122, 139, 140, 266 Least-Squares Analysis, 266, 289 Legionellosis, 176, 267 Lens, 159, 267 Lesion, 60, 242, 257, 267, 268, 301 Lethal, 50, 60, 267, 273 Lethargy, 260, 261, 267 Leucocyte, 226, 250, 267 Leukocyte Disorders, 177, 267 Leukocyte Elastase, 140, 267 Leukocytes, 20, 44, 61, 63, 140, 232, 234, 238, 257, 264, 267, 301 Leukotrienes, 25, 229, 248, 267, 268 Library Services, 218, 267 Life cycle, 239, 254, 267 Life Expectancy, 6, 94, 147, 267 Ligament, 176, 267, 280, 285 Ligands, 164, 267 Ligase, 29, 267 Likelihood Functions, 267, 289 Linear Models, 267, 289 Linkage, 14, 29, 30, 255, 267, 268, 279 Linkage Disequilibrium, 30, 268 Lipid, 32, 54, 153, 229, 256, 264, 266, 268, 273, 277, 300 Lipid Peroxidation, 268, 277 Lipopolysaccharide, 32, 257, 268 Lipoprotein, 58, 257, 268, 269 Lipoxygenase, 138, 229, 267, 268 Lipoxygenase Inhibitors, 138, 268 Liver scan, 268, 292 Living will, 167, 268 Localization, 60, 124, 262, 268 Localized, 61, 234, 245, 253, 258, 263, 266, 268, 281, 292, 301 Logistic Models, 268, 289 Longitudinal Studies, 129, 243, 268 Long-Term Care, 61, 268 Loop, 259, 268 Loss of Heterozygosity, 39, 268 Low-density lipoprotein, 268, 269 Lower Esophageal Sphincter, 175, 254, 255, 269 Lucida, 266, 269 Lumbar, 68, 269 Lumen, 235, 251, 269 Lung Transplantation, 46, 51, 64, 65, 86, 92, 94, 269 Lung volume, 33, 51, 269, 290 Lupus, 60, 168, 187, 209, 269, 297 Lymph, 223, 249, 259, 269, 291

Lymph node, 269, 291 Lymphatic, 249, 263, 269, 271, 294, 295, 299 Lymphocyte, 12, 37, 42, 53, 60, 228, 269, 270 Lymphocytic, 6, 16, 269 Lymphoid, 60, 145, 228, 267, 269 Lymphoma, 6, 143, 269 Lysine, 246, 260, 266, 269, 300 M Macrophage, 12, 16, 23, 31, 41, 42, 62, 65, 264, 269 Magnetic Resonance Imaging, 269, 292 Major Histocompatibility Complex, 257, 269 Malabsorption, 237, 270 Malformation, 88, 270 Malignant, 6, 89, 152, 223, 228, 234, 270, 274 Malnutrition, 140, 225, 231, 270 Mammary, 242, 270 Matrix metalloproteinase, 73, 91, 270 Mechanical ventilation, 17, 36, 66, 121, 146, 235, 270 Mechanoreceptors, 270, 290 Medial, 46, 230, 270 Mediate, 19, 43, 50, 247, 270, 288 Mediator, 43, 63, 264, 270, 282 Medical Records, 270, 291 Medical Staff, 247, 270 MEDLINE, 197, 270 Melanin, 270, 280, 301 Membrane Fusion, 227, 270 Membrane Glycoproteins, 270 Membrane Proteins, 270, 286 Memory, 245, 270 Meninges, 238, 243, 271 Meniscus, 144, 271 Menopause, 271, 283 Mental Disorders, 135, 271, 287 Mental Health, iv, 9, 135, 167, 168, 196, 199, 271, 287 Mental Health Services, iv, 9, 167, 199, 271 Mental Retardation, 39, 271 Mentors, 55, 271 Mercury, 20, 253, 271 Mesenchymal, 23, 25, 26, 271 Metabolic disorder, 207, 256, 271 Metastasis, 270, 271 Metastatic, 161, 234, 271 Methyltransferase, 60, 271 MI, 148, 222, 271

Index 315

Mice Minute Virus, 271, 279 Microbe, 52, 271, 299 Microbiological, 32, 271 Microbiology, 28, 55, 105, 151, 174, 223, 231, 271 Microcirculation, 271, 281 Microorganism, 240, 272, 279, 303 Micro-organism, 245, 272 Microscopy, 15, 52, 171, 209, 232, 272 Migration, 61, 272 Mineralocorticoids, 224, 243, 272 Mitochondrial Swelling, 272, 274 Mitosis, 229, 272 Mobility, 139, 272 Mobilization, 82, 272 Mode of Transmission, 209, 272 Modification, 53, 147, 272, 288 Modulator, 35, 272 Monitor, 32, 54, 105, 127, 162, 243, 272, 276 Monoclonal, 7, 43, 60, 260, 272 Monocyte, 31, 272 Monogenic, 27, 272 Mononuclear, 8, 26, 257, 272, 301 Morphine, 99, 115, 272, 274, 276 Motility, 8, 161, 187, 273 Mucinous, 93, 273 Mucociliary, 45, 50, 144, 273, 293 Mucociliary Clearance, 50, 273 Mucolytic, 234, 273 Mucosa, 150, 158, 237, 250, 269, 273 Mucositis, 164, 273 Mucus, 20, 141, 142, 152, 154, 159, 273 Multiple sclerosis, 151, 273 Muscarinic Agonists, 239, 273 Muscle Contraction, 273, 292 Muscle Hypertonia, 273, 275 Mustard Gas, 266, 273 Myalgia, 263, 273 Mydriatic, 247, 273 Myelin, 273 Myocardial infarction, 5, 232, 243, 271, 273, 303 Myocarditis, 209, 273 Myocardium, 209, 271, 273 Myopathy, 8, 273 Myositis, 69, 274 N Naphthols, 138, 274 Narcotic, 272, 274, 275 Nasal Mucosa, 263, 274 Nasal Polyps, 151, 274 Nasogastric, 249, 274

Nasopharynx, 66, 91, 274 Nausea, 274, 278, 301 NCI, 1, 134, 195, 274 Nebulizer, 123, 126, 159, 274 Necrosis, 65, 229, 238, 263, 271, 273, 274, 291, 293 Need, 3, 7, 36, 46, 48, 64, 141, 149, 150, 153, 155, 159, 167, 175, 186, 191, 198, 208, 213, 224, 239, 270, 274, 299 Neonatology, 10, 36, 78, 85, 274 Neoplasm, 6, 274 Neoplastic, 170, 171, 173, 260, 269, 274 Nephritis, 60, 274 Nephropathy, 266, 274 Nephrosis, 274 Nephrotic, 7, 274 Nerve, 224, 227, 230, 245, 252, 270, 273, 274, 275, 279, 280, 283, 284, 290, 291, 292, 296, 300, 302 Nervous System, 238, 270, 274, 275, 280, 297 Networks, 49, 274 Neural, 109, 259, 270, 275, 290 Neuroendocrine, 43, 275 Neurologic, 175, 260, 275 Neuromuscular, 177, 188, 223, 275, 301 Neuromuscular Diseases, 177, 275 Neuromuscular Junction, 223, 275 Neurons, 239, 245, 251, 254, 275, 297 Neurophysiology, 246, 275 Neutrophil, 16, 41, 44, 61, 65, 76, 105, 110, 140, 207, 225, 275 Neutrophil Infiltration, 61, 275 Nickel, 114, 275 Nicotine, 43, 275 Nitric Oxide, 17, 33, 35, 36, 59, 63, 80, 82, 102, 121, 155, 156, 171, 275 Nitrogen, 13, 98, 149, 225, 227, 244, 252, 253, 275, 278, 300 Nitrogen Dioxide, 13, 275 Nitrous Oxide, 132, 275 Nonmalignant, 90, 275 Norepinephrine, 224, 247, 275 Nuclear, 24, 83, 121, 164, 171, 172, 249, 251, 274, 276 Nuclear Medicine, 83, 121, 171, 172, 276 Nucleic acid, 142, 161, 231, 244, 255, 262, 275, 276, 287 Nucleus, 229, 230, 232, 239, 244, 246, 251, 272, 276, 286, 296 Nutritional Status, 3, 276 Nutritional Support, 91, 128, 146, 255, 276

316 Lung Disease

O Observational study, 51, 276 Occupational Exposure, 124, 276 Odour, 229, 276, 301 Oncogene, 143, 259, 276 Opacity, 245, 276 Opium, 272, 276 Oral Health, 3, 176, 186, 276 Osmotic, 225, 272, 276 Osteoporosis, 168, 276 Outpatient, 6, 132, 277 Ovalbumin, 17, 277 Ovaries, 277, 289 Ovary, 277, 282 Overweight, 6, 115, 277 Ovum, 255, 267, 277, 284 Oxaliplatin, 81, 114, 277 Oxidants, 38, 40, 58, 140, 277 Oxidation, 54, 140, 223, 228, 229, 244, 256, 268, 277 Oxidation-Reduction, 277 Oxidative metabolism, 267, 277 Oxidative Stress, 40, 53, 105, 277 Oxygen Consumption, 251, 277, 290 Oxygenase, 26, 43, 277 Oxygenation, 19, 36, 48, 52, 55, 65, 73, 139, 148, 149, 160, 261, 277 P Paediatric, 68, 76, 89, 99, 111, 277 Palate, 239, 274, 277 Palliative, 278, 298 Pancreas, 223, 233, 246, 254, 264, 278, 292, 300, 301 Pancreatic, 24, 27, 236, 254, 278 Pancreatic enzymes, 24, 278 Pancreatic Insufficiency, 27, 278 Pancreatic Juice, 254, 278 Pancreatitis, 25, 164, 278 Paneth Cells, 226, 278 Panic, 88, 278 Panic Disorder, 88, 278 Panniculitis, 207, 278 Paranasal Sinuses, 278, 293 Parenchyma, 153, 187, 278 Paresthesias, 278 Parietal, 278, 282 Parity, 6, 278 Parotid, 279, 291 Particle, 26, 39, 279, 294, 300 Parvovirus, 74, 271, 279 Pathogen, 12, 32, 149, 279

Pathologic, 7, 16, 54, 175, 181, 229, 233, 235, 242, 261, 279, 287, 290 Pathologic Processes, 229, 279 Pathophysiology, 8, 16, 17, 25, 27, 28, 30, 43, 58, 126, 171, 176, 279 Patient Education, 198, 206, 210, 216, 218, 222, 279 Patient Selection, 61, 279 Pelvic, 6, 176, 279, 285 Penicillamine, 187, 279 Penicillin, 66, 91, 228, 279, 302 Peptide, 23, 32, 43, 56, 58, 239, 250, 279, 283, 286, 296 Peptide Chain Elongation, 239, 279 Peptide T, 23, 58, 279 Perfusion, 55, 65, 261, 279 Pericarditis, 209, 279 Pericardium, 209, 279, 297 Perinatal, 10, 85, 98, 102, 109, 263, 279 Periodontal Attachment Loss, 4, 280 Periodontal disease, 4, 186, 280 Periodontal Ligament, 280 Periodontitis, 280 Perioperative, 55, 177, 280 Peripheral Nervous System, 275, 280, 296 Peripheral Nervous System Diseases, 275, 280 Perivascular, 8, 280 PH, 45, 146, 280 Phagocyte, 277, 280 Phagocytosis, 62, 280 Pharmacologic, 11, 25, 56, 227, 257, 280, 299 Pharynx, 6, 254, 263, 274, 280 Phenotype, 11, 24, 27, 28, 29, 32, 34, 39, 57, 58, 280 Phenyl, 138, 280 Phenylalanine, 27, 280, 301 Phospholipases, 280, 293 Phospholipids, 56, 69, 252, 263, 268, 280 Phosphorous, 146, 281 Phosphorus, 235, 281 Phosphorylation, 13, 244, 281 Photocoagulation, 240, 281 Physical Examination, 7, 177, 255, 281 Physiologic, 17, 22, 47, 128, 132, 146, 179, 225, 233, 246, 257, 281, 285, 289, 290 Physiology, 14, 39, 50, 62, 69, 91, 95, 101, 103, 104, 169, 171, 181, 223, 254, 275, 281 Pigment, 225, 232, 281 Pilot study, 36, 47, 66, 107, 281 Pituitary Gland, 243, 281

Index 317

Plants, 225, 234, 236, 245, 256, 276, 281, 282, 287, 291, 299 Plasma cells, 228, 281 Plasma protein, 140, 225, 281, 286 Plasmin, 281 Plasminogen, 44, 281 Plasminogen Activators, 44, 281 Platelet Activation, 282, 293 Platelet Aggregation, 142, 147, 227, 275, 282, 298 Platelet Factor 4, 264, 282 Platelets, 61, 209, 229, 232, 275, 282, 298 Platinum, 268, 277, 282 Platinum Compounds, 277, 282 Plethysmography, 51, 282 Pleura, 120, 282 Pleural, 7, 282 Pleural cavity, 282 Pleural Effusion, 7, 282 Pneumoconiosis, 132, 151, 282, 293 Pneumonitis, 7, 16, 60, 83, 187, 209, 235, 282 Pneumothorax, 123, 203, 204, 282 Poisoning, 20, 232, 235, 245, 248, 265, 271, 274, 282 Pollen, 17, 282 Polymerase, 15, 283 Polymerase Chain Reaction, 15, 283 Polymers, 144, 283, 286 Polymorphic, 27, 283 Polymorphism, 23, 34, 283 Polypeptide, 161, 226, 240, 253, 281, 283, 286, 304 Polyposis, 240, 283 Polysaccharide, 228, 283, 286 Posterior, 178, 226, 230, 238, 247, 278, 283, 292 Postmenopausal, 6, 276, 283 Postnatal, 17, 19, 43, 76, 79, 97, 103, 210, 283, 295 Postoperative, 92, 176, 283 Postsynaptic, 283, 293, 297 Post-translational, 58, 283 Potentiates, 264, 283 Potentiation, 283, 293 Practicability, 283, 300 Practice Guidelines, 199, 210, 283 Precancerous, 175, 284 Precipitating Factors, 237, 284 Preclinical, 33, 284 Precursor, 63, 229, 244, 247, 248, 250, 275, 280, 281, 284, 286, 300, 301, 302

Predisposition, 125, 163, 284 Prednisolone, 284 Prednisone, 25, 127, 284 Pregnancy Tests, 255, 284 Premalignant, 284 Prenatal, 35, 168, 249, 284 Prenatal Care, 168, 284 Prevalence, 6, 33, 35, 58, 124, 152, 168, 175, 187, 284 Probenecid, 8, 284 Procainamide, 60, 284 Procaine, 284 Progesterone, 284, 295 Prognostic factor, 46, 284, 297 Programmed Instruction, 180, 284 Progression, 13, 24, 32, 34, 37, 79, 105, 121, 122, 124, 153, 154, 227, 244, 285 Projection, 245, 276, 285 Prokinetic Drugs, 175, 285 Prolapse, 6, 176, 285 Proline, 56, 57, 240, 260, 285 Promoter, 23, 24, 25, 34, 42, 285 Prone, 210, 285 Prophylaxis, 47, 152, 198, 285, 303 Proportional, 107, 285 Prospective study, 29, 111, 285 Prostaglandin, 25, 285, 298 Prostaglandins A, 285 Prostate, 58, 233, 285, 301 Prostheses and Implants, 230, 286 Protease, 17, 42, 44, 50, 67, 226, 286 Protein C, 56, 140, 150, 225, 226, 229, 268, 286, 301 Protein Conformation, 226, 286 Protein Isoforms, 9, 226, 286 Protein S, 146, 173, 233, 239, 251, 255, 286, 291 Proteinuria, 7, 286 Proteoglycans, 172, 232, 252, 286 Proteolytic, 56, 225, 226, 241, 250, 253, 281, 286 Prothrombin, 4, 286, 298 Prothrombin Time, 4, 286 Protocol, 12, 65, 122, 286 Proton Pump, 175, 286 Protons, 260, 265, 286, 288 Protozoa, 271, 272, 286 Proximal, 247, 287 Pruritic, 248, 287 Pseudomonas, 32, 34, 42, 62, 67, 145, 158, 287 Psoriasis, 138, 151, 273, 287

318 Lung Disease

Psychiatry, 253, 287, 302 Psychic, 287, 292 Psychomotor, 245, 287 Public Health, 13, 20, 29, 38, 41, 58, 114, 168, 181, 199, 209, 287 Public Policy, 197, 287 Publishing, 7, 66, 177, 287 Pulmonary Artery, 46, 233, 287, 303 Pulmonary Circulation, 17, 61, 172, 287 Pulmonary Edema, 7, 126, 204, 239, 287 Pulmonary Embolism, 287, 303 Pulmonary Gas Exchange, 139, 287 Pulmonary hypertension, 36, 45, 48, 55, 68, 70, 107, 187, 209, 287 Pulmonary Ventilation, 287, 290 Pulse, 59, 107, 127, 272, 287 Pupil, 242, 247, 273, 287 Purines, 231, 287, 293 Purulent, 147, 223, 288 Pyridoxal, 288, 299 Q Quality of Life, 48, 51, 97, 112, 128, 131, 133, 139, 153, 288 Quiescent, 37, 288 R Race, 4, 147, 272, 288 Radiation, 250, 254, 265, 288, 292, 304 Radioactive, 65, 234, 257, 260, 268, 273, 276, 288, 292 Radiography, 98, 202, 255, 288 Radiologist, 157, 288 Radiology, 33, 41, 79, 89, 97, 98, 104, 107, 109, 110, 114, 181, 202, 276, 288 Radionuclide Imaging, 177, 288 Randomized, 36, 47, 48, 57, 66, 96, 128, 130, 131, 132, 248, 288 Randomized clinical trial, 48, 57, 288 Ranitidine, 8, 288 Rarefaction, 107, 288 Reabsorption, 144, 284, 288 Reactive Oxygen Species, 13, 39, 288 Reagent, 239, 260, 288 Recombinant, 17, 23, 31, 59, 289, 302 Recombinant Proteins, 59, 289 Recombination, 255, 289 Rectum, 229, 234, 240, 246, 247, 253, 254, 262, 263, 266, 285, 289 Red blood cells, 251, 277, 289, 291 Reductase, 289, 298 Refer, 1, 235, 240, 247, 253, 254, 268, 289 Reflex, 289, 290 Reflux, 85, 175, 205, 254, 255, 289

Refraction, 289, 295 Regimen, 15, 48, 107, 163, 184, 185, 248, 289 Registries, 20, 289 Regression Analysis, 5, 62, 289 Regurgitation, 254, 258, 289 Relaxin, 187, 289 Reliability, 64, 289 Renal failure, 232, 245, 289 Renal tubular, 284, 289 Research Design, 41, 289 Resection, 95, 106, 289 Resorption, 260, 288, 290 Respirable, 211, 290 Respiration, 77, 88, 92, 93, 99, 125, 139, 172, 229, 236, 272, 277, 290 Respirator, 270, 290, 303 Respiratory distress syndrome, 45, 110, 146, 176, 235, 290 Respiratory failure, 4, 27, 36, 66, 126, 129, 174, 290, 303 Respiratory Mechanics, 51, 290 Respiratory Physiology, 69, 75, 77, 79, 81, 82, 84, 94, 96, 97, 98, 106, 290, 302 Respiratory syncytial virus, 105, 110, 112, 290 Respiratory System, 79, 205, 225, 273, 290 Respiratory Therapy, 180, 290 Restless legs, 208, 290 Resuscitation, 290 Retina, 242, 267, 290, 291, 302 Retinal, 247, 290 Retinoblastoma, 13, 290 Retinoid, 33, 164, 291 Retrospective, 3, 4, 6, 29, 53, 65, 291 Retrospective study, 3, 291 Rheumatic Diseases, 37, 93, 177, 187, 291 Rheumatism, 80, 93, 291 Rheumatoid, 83, 106, 120, 121, 151, 240, 277, 291 Rheumatoid arthritis, 83, 120, 121, 151, 240, 291 Rhinitis, 77, 152, 291 Ribonucleoside Diphosphate Reductase, 260, 291 Ribose, 223, 244, 291 Ribosome, 291, 300 Risk factor, 7, 13, 34, 54, 65, 81, 102, 125, 127, 133, 185, 208, 237, 250, 268, 285, 291 Rod, 231, 287, 291 Rubber, 274, 291

Index 319

S Saline, 122, 234, 291 Salivary, 246, 291 Salivary glands, 246, 291 Salivation, 251, 291 Saphenous, 242, 291 Saphenous Vein, 242, 291 Saponins, 291, 295 Sarcoidosis, 121, 127, 176, 177, 291 Sarcoplasmic Reticulum, 56, 292 Scans, 121, 292 Schizophrenia, 248, 292, 304 Sclera, 241, 242, 292, 302 Scleroderma, 54, 80, 93, 102, 118, 122, 129, 187, 292 Sclerosis, 39, 93, 107, 122, 129, 151, 176, 185, 230, 240, 273, 292 Screening, 24, 59, 157, 198, 207, 240, 292, 301 Sebaceous, 266, 292 Sebaceous gland, 266, 292 Secretion, 12, 32, 52, 56, 101, 117, 142, 158, 159, 224, 243, 259, 260, 261, 264, 272, 273, 278, 288, 291, 292, 300, 302 Secretory, 17, 18, 56, 58, 67, 142, 226, 273, 292, 297 Sediment, 292, 301 Segregation, 29, 231, 289, 292 Seizures, 39, 245, 292 Selenium, 57, 292 Selenomethionine, 57, 292 Self Care, 208, 223, 292 Semen, 285, 292 Semisynthetic, 239, 292 Senile, 276, 292 Sensitization, 12, 24, 56, 77, 84, 293 Septic, 71, 293 Sequence Homology, 279, 293 Sequencing, 148, 283, 293 Sequester, 44, 293 Serine, 44, 50, 293, 296, 300 Serous, 249, 282, 293 Serum, 4, 36, 38, 43, 58, 73, 74, 105, 139, 140, 224, 225, 227, 232, 240, 241, 261, 269, 272, 293, 301 Shock, 236, 260, 293, 300 Shunt, 105, 293 Side effect, 36, 147, 188, 189, 191, 224, 233, 244, 293, 299 Signal Transduction, 54, 161, 227, 263, 293 Signs and Symptoms, 5, 207, 293, 301 Silicosis, 132, 142, 211, 293

Sinusitis, 176, 293 Skeletal, 164, 227, 273, 292, 294 Skeleton, 266, 285, 294 Skull, 243, 294, 298 Sleep apnea, 176, 294 Small intestine, 6, 232, 239, 248, 250, 259, 265, 274, 294, 300, 303 Smooth muscle, 17, 39, 41, 46, 48, 56, 142, 227, 235, 242, 259, 272, 273, 294, 296 Social Environment, 288, 294 Sodium, 50, 256, 272, 288, 294, 297 Soft tissue, 234, 294 Solid tumor, 227, 233, 294 Solvent, 144, 232, 256, 276, 294 Soma, 294 Somatic, 16, 40, 259, 272, 280, 294 Sound wave, 241, 288, 294 Spasm, 275, 294 Spasmogenic, 227, 294 Specialist, 212, 247, 294 Specific immune cells, 16, 294 Specificity, 38, 44, 157, 224, 229, 267, 295, 296 Spectrum, 52, 185, 295 Sperm, 227, 239, 282, 295 Sphincter, 175, 266, 295 Spinal cord, 234, 238, 239, 243, 250, 271, 274, 280, 289, 295 Spinal Stenosis, 68, 295 Spirochete, 295, 297 Spirometry, 65, 163, 202, 295 Spleen, 269, 291, 295 Sporadic, 39, 290, 295 Sputum, 141, 157, 158, 159, 209, 295 Staging, 129, 292, 295 Stem cell transplantation, 185, 295 Stem Cells, 295 Sterile, 122, 295 Sterility, 244, 295 Sterilization, 144, 295 Steroid, 16, 152, 243, 291, 295 Stilbenes, 151, 295 Stimulant, 235, 259, 295, 302 Stimulus, 35, 247, 248, 251, 264, 265, 266, 278, 289, 296, 298 Stomach, 145, 223, 231, 246, 247, 251, 254, 255, 259, 266, 269, 274, 280, 289, 294, 295, 296 Stool, 262, 266, 296 Strand, 283, 296 Streptomyces, 18, 233, 251, 296

320 Lung Disease

Stress, 4, 16, 40, 53, 101, 126, 149, 153, 168, 208, 243, 274, 277, 284, 291, 296 Stricture, 175, 296 Stroke, 5, 135, 168, 177, 196, 208, 236, 296 Stroma, 278, 296 Subacute, 22, 263, 293, 296 Subclinical, 6, 263, 292, 296 Subcutaneous, 149, 248, 278, 296 Subspecies, 294, 296 Substance P, 251, 292, 296 Substrate, 144, 250, 268, 296 Subtilisin, 18, 296 Suction, 160, 296 Sulfur, 252, 296 Supplementation, 57, 140, 296 Support group, 49, 296 Suppression, 63, 243, 296 Suppurative, 66, 73, 91, 296 Surfactant, 19, 21, 31, 35, 36, 56, 58, 59, 62, 68, 69, 74, 76, 79, 85, 126, 142, 162, 169, 173, 181, 297 Survival Analysis, 47, 297 Survival Rate, 4, 5, 121, 149, 297 Sweat, 28, 261, 297 Sweat Glands, 297 Symphysis, 285, 297 Symptomatic, 8, 122, 253, 278, 297 Synaptic, 275, 293, 297 Synaptic Transmission, 275, 297 Synergistic, 14, 297 Syphilis, 151, 297 Systemic disease, 4, 39, 297 Systemic lupus erythematosus, 60, 151, 209, 240, 297 Systems Analysis, 174, 297 Systolic, 261, 297 T Tear Gases, 266, 297 Telecommunications, 127, 298 Temporal, 15, 27, 298 Thalidomide, 187, 298 Therapeutics, 11, 34, 36, 41, 51, 123, 191, 298 Thermal, 230, 283, 298 Thioredoxin, 150, 298 Thoracic Surgery, 55, 78, 106, 111, 298 Thorax, 73, 81, 85, 95, 223, 269, 298 Threonine, 279, 293, 298 Threshold, 261, 298 Thrombin, 253, 282, 286, 298 Thrombocytes, 282, 298 Thrombolytic, 281, 298

Thrombomodulin, 286, 298 Thromboplastin, 286, 298 Thrombosis, 51, 80, 232, 265, 286, 296, 298 Thromboxanes, 229, 248, 298 Thrombus, 242, 263, 282, 298, 302 Thymus, 262, 269, 299 Thyroid, 83, 177, 261, 299, 301 Thyroid Gland, 299 Thyroiditis, 142, 299 Thyroiditis, Autoimmune, 142, 299 Thyroxine, 225, 280, 299 Tin, 208, 282, 299 Tolerance, 158, 223, 256, 299 Tomography, 109, 299 Tonicity, 50, 299 Tooth Loss, 186, 187, 299 Topical, 159, 230, 260, 299 Toxic, iv, 39, 52, 56, 58, 232, 250, 262, 275, 292, 299 Toxicity, 7, 35, 36, 39, 70, 78, 131, 164, 247, 271, 299 Toxicology, 21, 29, 67, 198, 299 Toxins, 23, 151, 228, 256, 263, 299 Trace element, 275, 299 Trachea, 51, 160, 234, 235, 266, 280, 299 Tracheoesophageal Fistula, 251, 299 Transaminase, 4, 299 Transcription Factors, 13, 24, 42, 299 Transduction, 293, 300 Transfection, 233, 300 Transfer Factor, 262, 300 Transforming Growth Factor beta, 23, 300 Translation, 198, 251, 300 Translational, 15, 31, 50, 64, 300 Translocation, 239, 251, 300 Transmitter, 223, 247, 265, 270, 276, 300 Transplantation, 46, 51, 64, 65, 71, 83, 86, 94, 96, 207, 239, 262, 269, 300 Trauma, 176, 181, 245, 251, 274, 278, 300 Treatment Outcome, 6, 300 Triglyceride, 261, 300 Trypsin, 206, 225, 250, 300 Tryptophan, 240, 300 Tuberous Sclerosis, 39, 123, 300 Tumor marker, 233, 300 Tumor Necrosis Factor, 65, 298, 301 Tumor suppressor gene, 39, 269, 301 Type 2 diabetes, 5, 301 Tyrosine, 57, 236, 247, 301 U Ulcer, 147, 301 Ultrasonography, 255, 301

Index 321

Umbilical Cord, 239, 301 Unconscious, 227, 245, 261, 301 Uracil, 301 Uraemia, 278, 301 Urea, 231, 297, 301 Urethra, 285, 301, 302 Uricosuric, 284, 301 Uridine Triphosphate, 141, 142, 301 Urinalysis, 7, 301 Urinary, 6, 58, 109, 231, 260, 262, 273, 301 Urine, 7, 43, 97, 121, 231, 232, 233, 243, 247, 258, 262, 286, 301, 302 Urine Testing, 7, 302 Uterus, 277, 284, 302 Uvea, 302 Uveitis, 178, 302 V Vaccine, 38, 145, 224, 226, 286, 302 Vacuoles, 249, 302 Vagina, 159, 246, 302 Vaginal, 6, 159, 176, 302 Valine, 279, 302 Valves, 177, 302 Vascular, 4, 5, 17, 26, 48, 56, 88, 89, 110, 142, 176, 238, 249, 263, 271, 275, 281, 298, 299, 302 Vascular Resistance, 48, 302 Vasculitis, 187, 238, 278, 302 Vasoactive, 48, 302 Vasoconstriction, 55, 250, 302 Vasodilators, 187, 275, 302 Vector, 23, 300, 302 Vein, 103, 107, 230, 265, 276, 279, 291, 301, 302 Venereal, 297, 302 Venous, 155, 230, 232, 238, 265, 286, 302, 303 Venous blood, 155, 238, 302

Venous Thrombosis, 232, 302, 303 Ventilation, 17, 21, 33, 55, 65, 89, 110, 111, 112, 133, 148, 302, 303 Ventilator, 36, 65, 130, 149, 270, 290, 303 Ventricle, 287, 297, 303 Ventricular, 70, 172, 253, 260, 303 Venules, 233, 235, 271, 303 Veterinary Medicine, 197, 303 Villi, 260, 303 Villous, 237, 303 Viral, 100, 149, 158, 176, 255, 263, 300, 303 Virulence, 149, 231, 299, 303 Virus, 74, 158, 168, 185, 190, 238, 255, 257, 290, 300, 303 Viscera, 294, 303 Viscosity, 52, 303 Vital Capacity, 109, 254, 303 Vitamin A, 263, 291, 303 Vitro, 13, 17, 23, 32, 38, 53, 59, 62, 258, 303 Vivo, 17, 30, 31, 33, 57, 59, 61, 66, 303 W Wakefulness, 245, 303 War, 257, 273, 303 Warfarin, 8, 303 White blood cell, 38, 207, 228, 267, 269, 272, 273, 275, 281, 303 Windpipe, 249, 280, 299, 304 Withdrawal, 245, 304 Wound Healing, 270, 304 X Xenograft, 227, 304 X-ray, 33, 121, 157, 202, 241, 254, 276, 288, 292, 304 Y Yeasts, 254, 280, 304 Z Zymogen, 286, 304

322 Lung Disease

Index 323

324 Lung Disease